# Patent

## Title
Biomarkers for prostate cancer and methods using the same

## Abstract

Methods for identifying and evaluating suites of biochemical and/or gene entities useful as biomarkers for early prediction of prostate cancer, disease grading, target identification/validation, and monitoring of drug efficacy are provided. Also provided are suites of small molecule entities as biomarkers for prostate cancer.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a National Stage application of International Application No. PCT/US2007/078805 filed Sep. 18, 2007, which claims the benefit of U.S. Provisional Application No. 60/845,600, filed Sep. 19, 2006, the entire contents of both of which are hereby incorporated herein by reference.


STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
This invention was made, in part, with Government support under Grant No. U01CA111275-01 from the National Institutes of Health. The U.S. Government may have certain rights in this invention.


FIELD
The invention generally relates to biomarkers for prostate cancer and methods based on the same biomarkers.
BACKGROUND
Prostate cancer is the leading cause of male cancer-related deaths and afflicts one out of nine men over the age of 65. The American Cancer Society estimates that over 200,000 American men will be diagnosed with prostate cancer and over 30,000 will die this year. While effective surgical and radiation treatments exist for localized prostate cancer, metastatic prostate cancer remains essentially incurable and most men diagnosed with metastatic disease will succumb over a period of months to years.
Prostate cancer is detected by either a digital rectal exam (DRE), or by the measurement of levels of prostate specific antigen (PSA), which has an unacceptably high rate of false-positives. The diagnosis of prostate cancer can be confirmed only by a biopsy. Radical prostatectomy, radiation and watchful waiting are generally effective for localized prostate cancer, but it is often difficult to determine which approach to use. Since it is not possible to distinguish between the indolent and more aggressive tumors current therapy takes a very conservative approach.
While imaging, X-rays, computerized tomography scans and further biopsies can help determine if prostate cancer has metastasized, they are not able to differentiate early stages. Understanding the progression of prostate cancer from a localized, early, indolent state, to an aggressive state, and, ultimately, to a metastatic state would allow the proper clinical management of this disease. Furthermore, early-indolent prostate cancer may be progressive or non-progressive toward aggressive forms.
SUMMARY
In one aspect, the present invention provides a method of diagnosing whether a subject has prostate cancer, comprising analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer in the sample, where the one or more biomarkers are selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 and comparing the level(s) of the one or more biomarkers in the sample to prostate cancer-positive and/or prostate cancer-negative reference levels of the one or more biomarkers in order to diagnose whether the subject has prostate cancer.
In another aspect, the present invention also provides a method of determining whether a subject is predisposed to developing prostate cancer, comprising analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer in the sample, where the one or more biomarkers are selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26; and comparing the level(s) of the one or more biomarkers in the sample to prostate cancer-positive and/or prostate cancer-negative reference levels of the one or more biomarkers in order to determine whether the subject is predisposed to developing prostate cancer.
In yet another aspect, the invention provides a method of monitoring progression/regression of prostate cancer in a subject comprising analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer in the sample, where the one or more biomarkers are selected from Tables 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 and the first sample is obtained from the subject at a first time point; analyzing a second biological sample from a subject to determine the level(s) of the one or more biomarkers, where the second sample is obtained from the subject at a second time point; and comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to monitor the progression/regression of prostate cancer in the subject.
In another aspect, the present invention provides a method of assessing the efficacy of a composition for treating prostate cancer comprising analyzing, from a subject having prostate cancer and currently or previously being treated with a composition, a biological sample to determine the level(s) of one or more biomarkers for prostate cancer selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26; and comparing the level(s) of the one or more biomarkers in the sample to (a) levels of the one or more biomarkers in a previously-taken biological sample from the subject, where the previously-taken biological sample was obtained from the subject before being treated with the composition, (b) prostate cancer-positive reference levels of the one or more biomarkers, and/or (c) prostate cancer-negative reference levels of the one or more biomarkers.
In another aspect, the present invention provides a method for assessing the efficacy of a composition in treating prostate cancer, comprising analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26, the first sample obtained from the subject at a first time point; administering the composition to the subject; analyzing a second biological sample from the subject to determine the level(s) of the one or more biomarkers, the second sample obtained from the subject at a second time point after administration of the composition; comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the efficacy of the composition for treating prostate cancer.
In yet another aspect, the invention provides a method of assessing the relative efficacy of two or more compositions for treating prostate cancer comprising analyzing, from a first subject having prostate cancer and currently or previously being treated with a first composition, a first biological sample to determine the level(s) of one or more biomarkers selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; analyzing, from a second subject having prostate cancer and currently or previously being treated with a second composition, a second biological sample to determine the level(s) of the one or more biomarkers; and comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the relative efficacy of the first and second compositions for treating prostate cancer.
In another aspect, the present invention provides a method for screening a composition for activity in modulating one or more biomarkers of prostate cancer, comprising contacting one or more cells with a composition; analyzing at least a portion of the one or more cells or a biological sample associated with the cells to determine the level(s) of one or more biomarkers of prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; and comparing the level(s) of the one or more biomarkers with predetermined standard levels for the biomarkers to determine whether the composition modulated the level(s) of the one or more biomarkers.
In a further aspect, the present invention provides a method for identifying a potential drug target for prostate cancer comprising identifying one or more biochemical pathways associated with one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; and identifying a protein affecting at least one of the one or more identified biochemical pathways, the protein being a potential drug target for prostate cancer.
In yet another aspect, the invention provides a method for treating a subject having prostate cancer comprising administering to the subject an effective amount of one or more biomarkers selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26 that are decreased in prostate cancer.
In another aspect, the invention also provides a method of distinguishing low grade prostate cancer from high grade prostate cancer in a subject having prostate cancer, comprising analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for low grade prostate cancer and/or high grade prostate cancer in the sample, where the one or more biomarkers are selected from Tables 3, 8, 11, 20 and/or 26 and comparing the level(s) of the one or more biomarkers in the sample to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or to high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer in order to determine whether the subject has low grade or high grade prostate cancer.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 provides an importance plot of one example of metabolites to distinguish Normal (N), Localized cancer tumor (T), and Metastatic tumor (M) tissue types.
FIG. 2 provides an importance plot of one example of metabolites to distinguish Normal prostate tissue (N) and Localized prostate tumor tissue (T).
FIG. 3 provides an importance plot of one example of metabolites to distinguish Non-cancer tissue (Control) and lower grade prostate cancer tissue (PCA) using urine samples.
FIG. 4 provides an importance plot of one example of metabolites to distinguish lower grade prostate cancer tissues and higher grade prostate cancer tissues from urine samples.
FIG. 5 provides an importance plot of one example of metabolites to distinguish non-cancer tissue (Control) and lower grade prostate cancer tissue (PCA) using plasma samples.
FIG. 6 provides an importance plot of one example of metabolites to distinguish lower grade prostate cancer tissues and higher grade prostate cancer tissues using plasma samples.
FIG. 7 provides an importance plot of one example of metabolites to distinguish subjects with lower grade prostate cancer and higher grade prostate cancer.



DETAILED DESCRIPTION
The present invention relates to biomarkers of prostate cancer, methods for diagnosis of prostate cancer, methods of distinguishing between low grade and high grade prostate cancer, methods of determining predisposition to prostate cancer, methods of monitoring progression/regression of prostate cancer, methods of assessing efficacy of compositions for treating prostate cancer, methods of screening compositions for activity in modulating biomarkers of prostate cancer, methods of treating prostate cancer, as well as other methods based on biomarkers of prostate cancer. Prior to describing this invention in further detail, however, the following terms will first be defined.
DEFINITIONS
“Biomarker” means a compound, preferably a metabolite, that is differentially present (i.e., increased or decreased) in a biological sample from a subject or a group of subjects having a first phenotype (e.g., having a disease) as compared to a biological sample from a subject or group of subjects having a second phenotype (e.g., not having the disease). A biomarker may be differentially present at any level, but is generally present at a level that is increased by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, by at least 100%, by at least 110%, by at least 120%, by at least 130%, by at least 140%, by at least 150%, or more; or is generally present at a level that is decreased by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, or by 100% (i.e., absent). A biomarker is preferably differentially present at a level that is statistically significant (i.e., a p-value less than 0.05 and/or a q-value of less than 0.10 as determined using either Welch's T-test or Wilcoxon's rank-sum Test).
The “level” of one or more biomarkers means the absolute or relative amount or concentration of the biomarker in the sample.
“Sample” or “biological sample” means biological material isolated from a subject. The biological sample may contain any biological material suitable for detecting the desired biomarkers, and may comprise cellular and/or non-cellular material from the subject. The sample can be isolated from any suitable biological tissue or fluid such as, for example, prostate tissue, blood, blood plasma, urine, or cerebral spinal fluid (CSF).
“Subject” means any animal, but is preferably a mammal, such as, for example, a human, monkey, mouse, or rabbit.
A “reference level” of a biomarker means a level of the biomarker that is indicative of a particular disease state, phenotype, or lack thereof, as well as combinations of disease states, phenotypes, or lack thereof. A “positive” reference level of a biomarker means a level that is indicative of a particular disease state or phenotype. A “negative” reference level of a biomarker means a level that is indicative of a lack of a particular disease state or phenotype. For example, a “prostate cancer-positive reference level” of a biomarker means a level of a biomarker that is indicative of a positive diagnosis of prostate cancer in a subject, and a “prostate cancer-negative reference level” of a biomarker means a level of a biomarker that is indicative of a negative diagnosis of prostate cancer in a subject. A “reference level” of a biomarker may be an absolute or relative amount or concentration of the biomarker, a presence or absence of the biomarker, a range of amount or concentration of the biomarker, a minimum and/or maximum amount or concentration of the biomarker, a mean amount or concentration of the biomarker, and/or a median amount or concentration of the biomarker; and, in addition, “reference levels” of combinations of biomarkers may also be ratios of absolute or relative amounts or concentrations of two or more biomarkers with respect to each other. Appropriate positive and negative reference levels of biomarkers for a particular disease state, phenotype, or lack thereof may be determined by measuring levels of desired biomarkers in one or more appropriate subjects, and such reference levels may be tailored to specific populations of subjects (e.g., a reference level may be age-matched so that comparisons may be made between biomarker levels in samples from subjects of a certain age and reference levels for a particular disease state, phenotype, or lack thereof in a certain age group). Such reference levels may also be tailored to specific techniques that are used to measure levels of biomarkers in biological samples (e.g., LC-MS, GC-MS, etc.), where the levels of biomarkers may differ based on the specific technique that is used.
“Non-biomarker compound” means a compound that is not differentially present in a biological sample from a subject or a group of subjects having a first phenotype (e.g., having a first disease) as compared to a biological sample from a subject or group of subjects having a second phenotype (e.g., not having the first disease). Such non-biomarker compounds may, however, be biomarkers in a biological sample from a subject or a group of subjects having a third phenotype (e.g., having a second disease) as compared to the first phenotype (e.g., having the first disease) or the second phenotype (e.g., not having the first disease).
“Metabolite”, or “small molecule”, means organic and inorganic molecules which are present in a cell. The term does not include large macromolecules, such as large proteins (e.g., proteins with molecular weights over 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, or 10,000), large nucleic acids (e.g., nucleic acids with molecular weights of over 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, or 10,000), or large polysaccharides (e.g., polysaccharides with a molecular weights of over 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, or 10,000). The small molecules of the cell are generally found free in solution in the cytoplasm or in other organelles, such as the mitochondria, where they form a pool of intermediates which can be metabolized further or used to generate large molecules, called macromolecules. The term “small molecules” includes signaling molecules and intermediates in the chemical reactions that transform energy derived from food into usable forms. Examples of small molecules include sugars, fatty acids, amino acids, nucleotides, intermediates formed during cellular processes, and other small molecules found within the cell.
“Metabolic profile”, or “small molecule profile”, means a complete or partial inventory of small molecules within a targeted cell, tissue, organ, organism, or fraction thereof (e.g., cellular compartment). The inventory may include the quantity and/or type of small molecules present. The “small molecule profile” may be determined using a single technique or multiple different techniques.
“Metabolome” means all of the small molecules present in a given organism.
“Prostate cancer” refers to a disease in which cancer develops in the prostate, a gland in the male reproductive system. “Low grade” or “lower grade” prostate cancer refers to non-metastatic prostate cancer, including malignant tumors with low potential for metastisis (i.e. prostate cancer that is considered to be less aggressive). “High grade” or “higher grade” prostate cancer refers to prostate cancer that has metastasized in a subject, including malignant tumors with high potential for metastisis (prostate cancer that is considered to be aggressive).
I. Biomarkers
The prostate cancer biomarkers described herein were discovered using metabolomic profiling techniques. Such metabolomic profiling techniques are described in more detail in the Examples set forth below as well as in U.S. Pat. No. 7,005,255 and U.S. patent application Ser. Nos. 11/357,732, 10/695,265 (Publication No. 2005/0014132), 11/301,077 (Publication No. 2006/0134676), 11/301,078 (Publication No. 2006/0134677), 11/301,079 (Publication No. 2006/0134678), and 11/405,033, the entire contents of which are hereby incorporated herein by reference.
Generally, metabolic profiles were determined for biological samples from human subjects diagnosed with prostate cancer as well as from one or more other groups of human subjects (e.g., healthy control subjects not diagnosed with prostate cancer), as well as from human subjects diagnosed with lower grade prostate cancer and human subjects diagnosed with metastatic/high grade prostate cancer. The metabolic profile for biological samples from a subject having prostate cancer was compared to the metabolic profile for biological samples from the one or more other groups of subjects. Those molecules differentially present, including those molecules differentially present at a level that is statistically significant, in the metabolic profile of samples from subjects with prostate cancer as compared to another group (e.g., healthy control subjects not diagnosed with prostate cancer) were identified as biomarkers to distinguish those groups. In addition, those molecules differentially present, including those molecules differentially present at a level that is statistically significant, in the metabolic profile of samples from subjects with low grade prostate cancer as compared to high grade prostate cancer were also identified as biomarkers to distinguish those groups.
The biomarkers are discussed in more detail herein. The biomarkers that were discovered correspond with the following group(s):

    
    
        Biomarkers for distinguishing subjects having prostate cancer vs. control subjects not diagnosed with prostate cancer (see Tables 1, 2, 4, 5, 6, 7, 9, 10, 15, 18, 22, 24);
        Biomarkers for distinguishing subjects having low grade prostate cancer vs. control subjects not diagnosed with prostate cancer (see Tables 1, 6, 9, 22);
        Biomarkers for distinguishing subjects having metastatic/high grade prostate cancer vs. control subjects not diagnosed with prostate cancer (see Tables 2, 7, 10, 24);
        Biomarkers for distinguishing subjects having metastatic/high grade prostate cancer vs. subjects having low grade prostate cancer (see Tables 3, 8, 11, 20, 26).
    
    


Although the identities of some of the biomarkers compounds are not known at this time, such identities are not necessary for the identification of the biomarkers in biological samples from subjects, as the “unnamed” compounds have been sufficiently characterized by analytical techniques to allow such identification. The analytical characterization of all such “unnamed” compounds is listed in the Examples. Such “unnamed” biomarkers are designated herein using the nomenclature “Metabolite” followed by a specific metabolite number.
IIA. Diagnosis of Prostate Cancer
The identification of biomarkers for prostate cancer allows for the diagnosis of (or for aiding in the diagnosis of) prostate cancer in subjects presenting one or more symptoms of prostate cancer. A method of diagnosing (or aiding in diagnosing) whether a subject has prostate cancer comprises (1) analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers of prostate cancer in the sample and (2) comparing the level(s) of the one or more biomarkers in the sample to prostate cancer-positive and/or prostate cancer-negative reference levels of the one or more biomarkers in order to diagnose (or aid in the diagnosis of) whether the subject has prostate cancer. The one or more biomarkers that are used are selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 and combinations thereof. When such a method is used to aid in the diagnosis of prostate cancer, the results of the method may be used along with other methods (or the results thereof) useful in the clinical determination of whether a subject has prostate cancer.
Any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample. Suitable methods include chromatography (e.g., HPLC, gas chromatography, liquid chromatography), mass spectrometry (e.g., MS, MS-MS), enzyme-linked immunosorbent assay (ELISA), antibody linkage, other immunochemical techniques, and combinations thereof. Further, the level(s) of the one or more biomarkers may be measured indirectly, for example, by using an assay that measures the level of a compound (or compounds) that correlates with the level of the biomarker(s) that are desired to be measured.
The levels of one or more of the biomarkers of Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 may be determined in the methods of diagnosing and methods of aiding in diagnosing whether a subject has prostate cancer. For example, the level(s) of one biomarker, two or more biomarkers, three or more biomarkers, four or more biomarkers, five or more biomarkers, six or more biomarkers, seven or more biomarkers, eight or more biomarkers, nine or more biomarkers, ten or more biomarkers, etc., including a combination of all of the biomarkers in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 or any fraction thereof, may be determined and used in such methods. Determining levels of combinations of the biomarkers may allow greater sensitivity and specificity in diagnosing prostate cancer and aiding in the diagnosis of prostate cancer, and may allow better differentiation of prostate cancer from other prostate disorders (e.g. benign prostatic hypertrophy (BPH), prostatitis, etc.) or other cancers that may have similar or overlapping biomarkers to prostate cancer (as compared to a subject not having prostate cancer). For example, ratios of the levels of certain biomarkers (and non-biomarker compounds) in biological samples may allow greater sensitivity and specificity in diagnosing prostate cancer and aiding in the diagnosis of prostate cancer and may allow better differentiation of prostate cancer from other cancers or other disorders of the prostate that may have similar or overlapping biomarkers to prostate cancer (as compared to a subject not having prostate cancer).
One or more biomarkers that are specific for diagnosing prostate cancer (or aiding in diagnosing prostate cancer) in a certain type of sample (e.g., prostate tissue sample, urine sample, or blood plasma sample) may also be used. For example, when the biological sample is prostate tissue, one or more biomarkers listed in Tables 1, 2, 13, and/or 15, may be used to diagnose (or aid in diagnosing) whether a subject has prostate cancer. When the biological sample is blood plasma, one or more biomarkers listed in Tables 4, 6, 7, 22, and/or 24 may be used to diagnose (or aid in diagnosing) whether a subject has prostate cancer. When the biological sample is urine, one or more biomarkers listed in Tables 5, 9, 10, and/or 18 may be used to diagnose (or aid in diagnosing) whether a subject has prostate cancer.
After the level(s) of the one or more biomarkers in the sample are determined, the level(s) are compared to prostate cancer-positive and/or prostate cancer-negative reference levels to aid in diagnosing or to diagnose whether the subject has prostate cancer. Levels of the one or more biomarkers in a sample matching the prostate cancer-positive reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of a diagnosis of prostate cancer in the subject. Levels of the one or more biomarkers in a sample matching the prostate cancer-negative reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of a diagnosis of no prostate cancer in the subject. In addition, levels of the one or more biomarkers that are differentially present (especially at a level that is statistically significant) in the sample as compared to prostate cancer-negative reference levels are indicative of a diagnosis of prostate cancer in the subject. Levels of the one or more biomarkers that are differentially present (especially at a level that is statistically significant) in the sample as compared to prostate cancer-positive reference levels are indicative of a diagnosis of no prostate cancer in the subject.
The level(s) of the one or more biomarkers may be compared to prostate cancer-positive and/or prostate cancer-negative reference levels using various techniques, including a simple comparison (e.g., a manual comparison) of the level(s) of the one or more biomarkers in the biological sample to prostate cancer-positive and/or prostate cancer-negative reference levels. The level(s) of the one or more biomarkers in the biological sample may also be compared to prostate cancer-positive and/or prostate cancer-negative reference levels using one or more statistical analyses (e.g., t-test, Welch's T-test, Wilcoxon's rank sum test, random forest).
In addition, the biological samples may be analyzed to determine the level(s) of one or more non-biomarker compounds. The level(s) of such non-biomarker compounds may also allow differentiation of prostate cancer from other prostate disorders that may have similar or overlapping biomarkers to prostate cancer (as compared to a subject not having a prostate disorder). For example, a known non-biomarker compound present in biological samples of subjects having prostate cancer and subjects not having prostate cancer could be monitored to verify a diagnosis of prostate cancer as compared to a diagnosis of another prostate disorder when biological samples from subjects having the prostate disorder do not have the non-biomarker compound.
The methods of diagnosing (or aiding in diagnosing) whether a subject has prostate cancer may also be conducted specifically to diagnose (or aid in diagnosing) whether a subject has low grade prostate cancer and/or high grade prostate cancer. Such methods comprise (1) analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers of low grade prostate cancer (and/or high grade prostate cancer) in the sample and (2) comparing the level(s) of the one or more biomarkers in the sample to low grade prostate cancer-positive and/or low grade prostate cancer-negative reference levels (or high grade prostate cancer-positive and/or high grade prostate cancer-negative reference levels) in order to diagnose (or aid in the diagnosis of) whether the subject has low grade prostate cancer (or high grade prostate cancer). Biomarker specific for low grade prostate cancer are listed in Tables 1, 6, 9, 22 and biomarkers specific for high grade prostate cancer are listed in Tables 2, 7, 10, 24.
IIB. Methods of Distinguishing Low Grade Prostate Cancer from High Grade Prostate Cancer
The identification of biomarkers for distinguishing low grade prostate cancer versus high grade prostate cancer allows low grade prostate cancer and high grade prostate cancer to be distinguished in patients. A method of distinguishing low grade prostate cancer from high grade prostate cancer in a subject having prostate cancer comprises (1) analyzing a biological sample from a subject to determine the level(s) in the sample of one or more biomarkers of low grade prostate cancer that distinguish over high grade prostate cancer and/or one or more biomarkers of high grade prostate cancer that distinguish over low grade prostate cancer, and (2) comparing the level(s) of the one or more biomarkers in the sample to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer of the one or more biomarkers in order to determine whether the subject has low grade or high grade prostate cancer. The one or more biomarkers that are used are selected from Tables 3, 8, 11, 20, and/or 26 and combinations thereof.
Any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample. Suitable methods include chromatography (e.g., HPLC, gas chromatography, liquid chromatography), mass spectrometry (e.g., MS, MS-MS), enzyme-linked immunosorbent assay (ELISA), antibody linkage, other immunochemical techniques, and combinations thereof. Further, the level(s) of the one or more biomarkers may be measured indirectly, for example, by using an assay that measures the level of a compound (or compounds) that correlates with the level of the biomarker(s) that are desired to be measured.
The levels of one or more of the biomarkers of Tables 3, 8, 11, 20, and/or 26 may be determined in the methods of diagnosing and methods of aiding in diagnosing whether a subject has prostate cancer. For example, the level(s) of one biomarker, two or more biomarkers, three or more biomarkers, four or more biomarkers, five or more biomarkers, six or more biomarkers, seven or more biomarkers, eight or more biomarkers, nine or more biomarkers, ten or more biomarkers, etc., including a combination of all of the biomarkers in Tables 3, 8, 11, 20, and/or 26 or any fraction thereof, may be determined and used in such methods. Determining levels of combinations of the biomarkers may allow greater sensitivity and specificity in distinguishing between low grade and high grade prostate cancer.
One or more biomarkers that are specific for distinguishing between low grade and high grade prostate cancer in a certain type of sample (e.g., prostate tissue sample, urine sample, or blood plasma sample) may also be used. For example, when the biological sample is prostate tissue, one or more biomarkers listed in Table 3 may be used. When the biological sample is blood plasma, one or more biomarkers listed in Table 8 or 26 may be used. When the biological sample is urine, one or more biomarkers listed in Table 11 or 20 may be used.
After the level(s) of the one or more biomarkers in the sample are determined, the level(s) are compared to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer-negative and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer of the one or more biomarkers in order to determine whether the subject has low grade or high grade prostate cancer. Levels of the one or more biomarkers in a sample matching the low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of low-grade prostate cancer in the subject. Levels of the one or more biomarkers in a sample matching the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of high-grade prostate cancer in the subject. If the level(s) of the one or more biomarkers are more similar to the low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels), then the results are indicative of low grade prostate cancer in the subject. If the level(s) of the one or more biomarkers are more similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer (or less similar to the low grade prostate cancer-positive reference levels), then the results are indicative of high grade prostate cancer in the subject.
The level(s) of the one or more biomarkers may be compared to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer using various techniques, including a simple comparison (e.g., a manual comparison) of the level(s) of the one or more biomarkers in the biological sample to low grade prostate cancer-positive and/or high grade prostate cancer-positive reference levels. The level(s) of the one or more biomarkers in the biological sample may also be compared to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer using one or more statistical analyses (e.g., t-test, Welch's T-test, Wilcoxon's rank sum test, random forest).
In addition, the biological samples may be analyzed to determine the level(s) of one or more non-biomarker compounds. The level(s) of such non-biomarker compounds may also allow differentiation of low grade prostate cancer from high grade prostate cancer.
III. Methods of Determining Predisposition to Prostate Cancer
The identification of biomarkers for prostate cancer also allows for the determination of whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer. A method of determining whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer comprises (1) analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers listed in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 in the sample and (2) comparing the level(s) of the one or more biomarkers in the sample to prostate cancer-positive and/or prostate cancer-negative reference levels of the one or more biomarkers in order to determine whether the subject is predisposed to developing prostate cancer. The results of the method may be used along with other methods (or the results thereof) useful in the clinical determination of whether a subject is predisposed to developing prostate cancer.
As described above in connection with methods of diagnosing (or aiding in the diagnosis of) prostate cancer, any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample.
As with the methods of diagnosing (or aiding in the diagnosis of) prostate cancer described above, the level(s) of one biomarker, two or more biomarkers, three or more biomarkers, four or more biomarkers, five or more biomarkers, six or more biomarkers, seven or more biomarkers, eight or more biomarkers, nine or more biomarkers, ten or more biomarkers, etc., including a combination of all of the biomarkers in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 or any fraction thereof, may be determined and used in methods of determining whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer.
After the level(s) of the one or more biomarkers in the sample are determined, the level(s) are compared to prostate cancer-positive and/or prostate cancer-negative reference levels in order to predict whether the subject is predisposed to developing prostate cancer. Levels of the one or more biomarkers in a sample matching the prostate cancer-positive reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the subject being predisposed to developing prostate cancer. Levels of the one or more biomarkers in a sample matching the prostate cancer-negative reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the subject not being predisposed to developing prostate cancer. In addition, levels of the one or more biomarkers that are differentially present (especially at a level that is statistically significant) in the sample as compared to prostate cancer-negative reference levels are indicative of the subject being predisposed to developing prostate cancer. Levels of the one or more biomarkers that are differentially present (especially at a level that is statistically significant) in the sample as compared to prostate cancer-positive reference levels are indicative of the subject not being predisposed to developing prostate cancer.
Furthermore, it may also be possible to determine reference levels specific to assessing whether or not a subject that does not have prostate cancer is predisposed to developing prostate cancer. For example, it may be possible to determine reference levels of the biomarkers for assessing different degrees of risk (e.g., low, medium, high) in a subject for developing prostate cancer. Such reference levels could be used for comparison to the levels of the one or more biomarkers in a biological sample from a subject.
As with the methods described above, the level(s) of the one or more biomarkers may be compared to prostate cancer-positive and/or prostate cancer-negative reference levels using various techniques, including a simple comparison, one or more statistical analyses, and combinations thereof.
As with the methods of diagnosing (or aiding in diagnosing) whether a subject has prostate cancer, the methods of determining whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer may further comprise analyzing the biological sample to determine the level(s) of one or more non-biomarker compounds.
The methods of determining whether a subject having no symptoms of prostate cancer is predisposed to developing prostate cancer may also be conducted specifically to determine whether a subject having no symptoms of prostate cancer is predisposed to developing low grade prostate cancer and/or high grade prostate cancer. Biomarker specific for low grade prostate cancer are listed in Tables 1, 6, 9, and 22 and biomarkers specific for high grade prostate cancer are listed in Tables 2, 7, 10, and 24.
In addition, methods of determining whether a subject having low grade prostate cancer is predisposed to developing high grade prostate cancer may be conducted using one or more biomarkers selected from Tables 3, 8, 11, 20, and 26.
IV. Methods of Monitoring Progression/Regression of Prostate Cancer
The identification of biomarkers for prostate cancer also allows for monitoring progression/regression of prostate cancer in a subject. A method of monitoring the progression/regression of prostate cancer in a subject comprises (1) analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26, the first sample obtained from the subject at a first time point, (2) analyzing a second biological sample from a subject to determine the level(s) of the one or more biomarkers, the second sample obtained from the subject at a second time point, and (3) comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to monitor the progression/regression of prostate cancer in the subject. The results of the method are indicative of the course of prostate cancer (i.e., progression or regression, if any change) in the subject.
The change (if any) in the level(s) of the one or more biomarkers over time may be indicative of progression or regression of prostate cancer in the subject. In order to characterize the course of prostate cancer in the subject, the level(s) of the one or more biomarkers in the first sample, the level(s) of the one or more biomarkers in the second sample, and/or the results of the comparison of the levels of the biomarkers in the first and second samples may be compared to prostate cancer-positive, prostate cancer-negative, low grade prostate cancer-positive, low grade prostate cancer-negative, high-grade prostate cancer-positive, and/or high grade prostate cancer-negative reference levels as well as low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer. If the comparisons indicate that the level(s) of the one or more biomarkers are increasing or decreasing over time (e.g., in the second sample as compared to the first sample) to become more similar to the prostate cancer-positive reference levels (or less similar to the prostate cancer-negative reference levels), to the high grade prostate cancer reference levels, or, when the subject initially has low grade prostate cancer, to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer, then the results are indicative of prostate cancer progression. If the comparisons indicate that the level(s) of the one or more biomarkers are increasing or decreasing over time to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels), or, when the subject initially has high grade prostate cancer, to low grade prostate cancer reference levels and/or to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, then the results are indicative of prostate cancer regression.
As with the other methods described herein, the comparisons made in the methods of monitoring progression/regression of prostate cancer in a subject may be carried out using various techniques, including simple comparisons, one or more statistical analyses, and combinations thereof.
The results of the method may be used along with other methods (or the results thereof) useful in the clinical monitoring of progression/regression of prostate cancer in a subject.
As described above in connection with methods of diagnosing (or aiding in the diagnosis of) prostate cancer, any suitable method may be used to analyze the biological samples in order to determine the level(s) of the one or more biomarkers in the samples. In addition, the level(s) one or more biomarkers, including a combination of all of the biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 or any fraction thereof, may be determined and used in methods of monitoring progression/regression of prostate cancer in a subject.
Such methods could be conducted to monitor the course of prostate cancer in subjects having prostate cancer or could be used in subjects not having prostate cancer (e.g., subjects suspected of being predisposed to developing prostate cancer) in order to monitor levels of predisposition to prostate cancer.
V. Methods of Assessing Efficacy of Compositions for Treating Prostate Cancer
The identification of biomarkers for prostate cancer also allows for assessment of the efficacy of a composition for treating prostate cancer as well as the assessment of the relative efficacy of two or more compositions for treating prostate cancer. Such assessments may be used, for example, in efficacy studies as well as in lead selection of compositions for treating prostate cancer.
A method of assessing the efficacy of a composition for treating prostate cancer comprises (1) analyzing, from a subject having prostate cancer and currently or previously being treated with a composition, a biological sample to determine the level(s) of one or more biomarkers selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26, and (2) comparing the level(s) of the one or more biomarkers in the sample to (a) level(s) of the one or more biomarkers in a previously-taken biological sample from the subject, wherein the previously-taken biological sample was obtained from the subject before being treated with the composition, (b) prostate cancer-positive reference levels (including low grade prostate cancer-positive and/or high grade prostate cancer-positive reference levels) of the one or more biomarkers, (c) prostate cancer-negative reference levels (including low grade prostate cancer-negative and/or high grade prostate cancer-negative reference levels) of the one or more biomarkers, (d) low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, and/or (e) high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer. The results of the comparison are indicative of the efficacy of the composition for treating prostate cancer.
Thus, in order to characterize the efficacy of the composition for treating prostate cancer, the level(s) of the one or more biomarkers in the biological sample are compared to (1) prostate cancer-positive reference levels, (2) prostate cancer-negative reference levels, (3) previous levels of the one or more biomarkers in the subject before treatment with the composition, (4) low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, and/or (5) high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer.
When comparing the level(s) of the one or more biomarkers in the biological sample (from a subject having prostate cancer and currently or previously being treated with a composition) to prostate cancer-positive reference levels and/or prostate cancer-negative reference levels, level(s) in the sample matching the prostate cancer-negative reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the composition having efficacy for treating prostate cancer. Levels of the one or more biomarkers in the sample matching the prostate cancer-positive reference levels (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the composition not having efficacy for treating prostate cancer. The comparisons may also indicate degrees of efficacy for treating prostate cancer based on the level(s) of the one or more biomarkers.
When comparing the level(s) of the one or more biomarkers in the biological sample (from a subject having high grade prostate cancer and currently or previously being treated with a composition) low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer, level(s) in the sample matching the low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the composition having efficacy for treating prostate cancer. Levels of the one or more biomarkers in the sample matching the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer (e.g., levels that are the same as the reference levels, substantially the same as the reference levels, above and/or below the minimum and/or maximum of the reference levels, and/or within the range of the reference levels) are indicative of the composition not having efficacy for treating prostate cancer.
When the level(s) of the one or more biomarkers in the biological sample (from a subject having prostate cancer and currently or previously being treated with a composition) are compared to level(s) of the one or more biomarkers in a previously-taken biological sample from the subject before treatment with the composition, any changes in the level(s) of the one or more biomarkers are indicative of the efficacy of the composition for treating prostate cancer. That is, if the comparisons indicate that the level(s) of the one or more biomarkers have increased or decreased after treatment with the composition to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels) or, when the subject initially has high grade prostate cancer, the level(s) have increased or decreased to become more similar to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer), then the results are indicative of the composition having efficacy for treating prostate cancer. If the comparisons indicate that the level(s) of the one or more biomarkers have not increased or decreased after treatment with the composition to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels) or, when the subject initially has high grade prostate cancer, the level(s) have not increased or decreased to become more similar to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer), then the results are indicative of the composition not having efficacy for treating prostate cancer. The comparisons may also indicate degrees of efficacy for treating prostate cancer based on the amount of changes observed in the level(s) of the one or more biomarkers after treatment. In order to help characterize such a comparison, the changes in the level(s) of the one or more biomarkers, the level(s) of the one or more biomarkers before treatment, and/or the level(s) of the one or more biomarkers in the subject currently or previously being treated with the composition may be compared to prostate cancer-positive reference levels (including low grade and high grade prostate cancer-positive reference levels), prostate cancer-negative reference levels (including low grade and high grade prostate cancer-negative reference levels), low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer.
Another method for assessing the efficacy of a composition in treating prostate cancer comprises (1) analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26, the first sample obtained from the subject at a first time point, (2) administering the composition to the subject, (3) analyzing a second biological sample from a subject to determine the level(s) of the one or more biomarkers, the second sample obtained from the subject at a second time point after administration of the composition, and (4) comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the efficacy of the composition for treating prostate cancer. As indicated above, if the comparison of the samples indicates that the level(s) of the one or more biomarkers have increased or decreased after administration of the composition to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels) or, when the subject initially has high grade prostate cancer, if the level(s) have increased or decreased to become more similar to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer), then the results are indicative of the composition having efficacy for treating prostate cancer. If the comparisons indicate that the level(s) of the one or more biomarkers have not increased or decreased after treatment with the composition to become more similar to the prostate cancer-negative reference levels (or less similar to the prostate cancer-positive reference levels) or, when the subject initially has high grade prostate cancer, the level(s) have not increased or decreased to become more similar to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer (or less similar to the high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer), then the results are indicative of the composition not having efficacy for treating prostate cancer. The comparison may also indicate a degree of efficacy for treating prostate cancer based on the amount of changes observed in the level(s) of the one or more biomarkers after administration of the composition as discussed above.
A method of assessing the relative efficacy of two or more compositions for treating prostate cancer comprises (1) analyzing, from a first subject having prostate cancer and currently or previously being treated with a first composition, a first biological sample to determine the level(s) of one or more biomarkers selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 (2) analyzing, from a second subject having prostate cancer and currently or previously being treated with a second composition, a second biological sample to determine the level(s) of the one or more biomarkers, and (3) comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the relative efficacy of the first and second compositions for treating prostate cancer. The results are indicative of the relative efficacy of the two compositions, and the results (or the levels of the one or more biomarkers in the first sample and/or the level(s) of the one or more biomarkers in the second sample) may be compared to prostate cancer-positive reference levels (including low grade and high grade prostate cancer-positive reference levels), prostate cancer-negative reference levels (including low grade and high grade prostate cancer-negative reference levels), low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer, and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer to aid in characterizing the relative efficacy.
Each of the methods of assessing efficacy may be conducted on one or more subjects or one or more groups of subjects (e.g., a first group being treated with a first composition and a second group being treated with a second composition).
As with the other methods described herein, the comparisons made in the methods of assessing efficacy (or relative efficacy) of compositions for treating prostate cancer may be carried out using various techniques, including simple comparisons, one or more statistical analyses, and combinations thereof. Any suitable method may be used to analyze the biological samples in order to determine the level(s) of the one or more biomarkers in the samples. In addition, the level(s) of one or more biomarkers, including a combination of all of the biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 or any fraction thereof, may be determined and used in methods of assessing efficacy (or relative efficacy) of compositions for treating prostate cancer.
Finally, the methods of assessing efficacy (or relative efficacy) of one or more compositions for treating prostate cancer may further comprise analyzing the biological sample to determine the level(s) of one or more non-biomarker compounds. The non-biomarker compounds may then be compared to reference levels of non-biomarker compounds for subjects having (or not having) prostate cancer.
VI. Methods of Screening a Composition for Activity in Modulating Biomarkers Associated with Prostate Cancer
The identification of biomarkers for prostate cancer also allows for the screening of compositions for activity in modulating biomarkers associated with prostate cancer, which may be useful in treating prostate cancer. Methods of screening compositions useful for treatment of prostate cancer comprise assaying test compositions for activity in modulating the levels of one or more biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26. Such screening assays may be conducted in vitro and/or in vivo, and may be in any form known in the art useful for assaying modulation of such biomarkers in the presence of a test composition such as, for example, cell culture assays, organ culture assays, and in vivo assays (e.g., assays involving animal models).
In one embodiment, a method for screening a composition for activity in modulating one or more biomarkers of prostate cancer comprises (1) contacting one or more cells with a composition, (2) analyzing at least a portion of the one or more cells or a biological sample associated with the cells to determine the level(s) of one or more biomarkers of prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; and (3) comparing the level(s) of the one or more biomarkers with predetermined standard levels for the one or more biomarkers to determine whether the composition modulated the level(s) of the one or more biomarkers. As discussed above, the cells may be contacted with the composition in vitro and/or in vivo. The predetermined standard levels for the one or more biomarkers may be the levels of the one or more biomarkers in the one or more cells in the absence of the composition. The predetermined standard levels for the one or more biomarkers may also be the level(s) of the one or more biomarkers in control cells not contacted with the composition.
In addition, the methods may further comprise analyzing at least a portion of the one or more cells or a biological sample associated with the cells to determine the level(s) of one or more non-biomarker compounds of prostate cancer. The levels of the non-biomarker compounds may then be compared to predetermined standard levels of the one or more non-biomarker compounds.
Any suitable method may be used to analyze at least a portion of the one or more cells or a biological sample associated with the cells in order to determine the level(s) of the one or more biomarkers (or levels of non-biomarker compounds). Suitable methods include chromatography (e.g., HPLC, gas chromatograph, liquid chromatography), mass spectrometry (e.g., MS, MS-MS), ELISA, antibody linkage, other immunochemical techniques, and combinations thereof. Further, the level(s) of the one or more biomarkers (or levels of non-biomarker compounds) may be measured indirectly, for example, by using an assay that measures the level of a compound (or compounds) that correlates with the level of the biomarker(s) (or non-biomarker compounds) that are desired to be measured.
VII. Method of Identifying Potential Drug Targets
The identification of biomarkers for prostate cancer also allows for the identification of potential drug targets for prostate cancer. A method for identifying a potential drug target for prostate cancer comprises (1) identifying one or more biochemical pathways associated with one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 and (2) identifying a protein (e.g., an enzyme) affecting at least one of the one or more identified biochemical pathways, the protein being a potential drug target for prostate cancer.
Another method for identifying a potential drug target for prostate cancer comprises (1) identifying one or more biochemical pathways associated with one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 and one or more non-biomarker compounds of prostate cancer and (2) identifying a protein affecting at least one of the one or more identified biochemical pathways, the protein being a potential drug target for prostate cancer.
One or more biochemical pathways (e.g., biosynthetic and/or metabolic (catabolic) pathway) are identified that are associated with one or more biomarkers (or non-biomarker compounds). After the biochemical pathways are identified, one or more proteins affecting at least one of the pathways are identified. Preferably, those proteins affecting more than one of the pathways are identified.
A build-up of one metabolite (e.g., a pathway intermediate) may indicate the presence of a ‘block’ downstream of the metabolite and the block may result in a low/absent level of a downstream metabolite (e.g. product of a biosynthetic pathway). In a similar manner, the absence of a metabolite could indicate the presence of a ‘block’ in the pathway upstream of the metabolite resulting from inactive or non-functional enzyme(s) or from unavailability of biochemical intermediates that are required substrates to produce the product. Alternatively, an increase in the level of a metabolite could indicate a genetic mutation that produces an aberrant protein which results in the over-production and/or accumulation of a metabolite which then leads to an alteration of other related biochemical pathways and result in dysregulation of the normal flux through the pathway; further, the build-up of the biochemical intermediate metabolite may be toxic or may compromise the production of a necessary intermediate for a related pathway. It is possible that the relationship between pathways is currently unknown and this data could reveal such a relationship.
For example, the data indicates that metabolites in the biochemical pathways involving nitrogen excretion, amino acid metabolism, energy metabolism, oxidative stress, purine metabolism and bile acid metabolism are enriched in prostate cancer subjects. Further, polyamine levels are higher in cancer subjects, which indicates that the level and/or activity of the enzyme ornithine decarboxylase is increased. It is known that polyamines can act as mitotic agents and have been associated with free radical damage. These observations indicate that the pathways leading to the production of polyamines (or to any of the aberrant biomarkers) would provide a number of potential targets useful for drug discovery.
The proteins identified as potential drug targets may then be used to identify compositions that may be potential candidates for treating prostate cancer, including compositions for gene therapy.
VIII. Methods of Treating Prostate Cancer
The identification of biomarkers for prostate cancer also allows for the treatment of prostate cancer. For example, in order to treat a subject having prostate cancer, an effective amount of one or more prostate cancer biomarkers that are lowered in prostate cancer as compared to a healthy subject not having prostate cancer may be administered to the subject. The biomarkers that may be administered may comprise one or more of the biomarkers in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26 that are decreased in prostate cancer. In some embodiments, the biomarkers that are administered are one or more biomarkers listed in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 20, 22, 24, and/or 26 that are decreased in prostate cancer and that have a p-value less than 0.10. In other embodiments, the biomarkers that are administered are one or biomarkers listed in Tables 1, 2 and/or 3 that are decreased in prostate cancer by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, or by 100% (i.e., absent).
IX. Methods of Using the Prostate Cancer Biomarkers for Other Types of Prostate Cancer
It is believed that some of the biomarkers for major prostate cancer described herein may also be biomarkers for other types of cancer, including, for example, lung cancer or kidney cancer. Therefore, it is believed that at least some of the prostate cancer biomarkers may be used in the methods described herein for other types of cancer. That is, the methods described herein with respect to prostate cancer may also be used for diagnosing (or aiding in the diagnosis of) any type of cancer, methods of monitoring progression/regression of any type of cancer, methods of assessing efficacy of compositions for treating any type of cancer, methods of screening a composition for activity in modulating biomarkers associated with any type of cancer, methods of identifying potential drug targets for any type of cancer, and methods of treating any type of cancer. Such methods could be conducted as described herein with respect to prostate cancer.
X. Methods of Using the Prostate Cancer Biomarkers for Other Prostate Disorders
It is believed that some of the biomarkers for prostate cancer described herein may also be biomarkers for prostate disorders (e.g. prostatitis, benign prostate hypertrophy (BHP)) in general. Therefore, it is believed that at least some of the prostate cancer biomarkers may be used in the methods described herein for prostate disorders in general. That is, the methods described herein with respect to prostate cancer may also be used for diagnosing (or aiding in the diagnosis of) a prostate disorder, methods of monitoring progression/regression of a prostate disorder, methods of assessing efficacy of compositions for treating a prostate disorder, methods of screening a composition for activity in modulating biomarkers associated with a prostate disorder, methods of identifying potential drug targets for prostate disorder, and methods of treating a prostate disorder. Such methods could be conducted as described herein with respect to prostate cancer.
XI. Other Methods
Other methods of using the biomarkers discussed herein are also contemplated. For example, the methods described in U.S. Pat. No. 7,005,255 and U.S. patent application Ser. No. 10/695,265 may be conducted using a small molecule profile comprising one or more of the biomarkers disclosed herein.
In any of the methods listed herein, the biomarkers that are used may be selected from those biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 having p-values of less than 0.05 and/or those biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 having q-values of less than 0.10. The biomarkers that are used in any of the methods described herein may also be selected from those biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 that are decreased in prostate cancer (as compared to the control) or that are decreased in remission (as compared to control or prostate cancer) by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, or by 100% (i.e., absent); and/or those biomarkers in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 that are increased in prostate cancer (as compared to the control or remission) or that are increased in remission (as compared to the control or prostate cancer) by at least 5%, by at least 10%, by at least 15%, by at least 20%, by at least 25%, by at least 30%, by at least 35%, by at least 40%, by at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by at least 85%, by at least 90%, by at least 95%, by at least 100%, by at least 110%, by at least 120%, by at least 130%, by at least 140%, by at least 150%, or more.
EXAMPLES
The invention will be further explained by the following illustrative examples that are intended to be non-limiting.
I. General Methods
A. Identification of Metabolic Profiles for Prostate Cancer
Each sample was analyzed to determine the concentration of several hundred metabolites. Analytical techniques such as GC-MS (gas chromatography-mass spectrometry) and LC-MS (liquid chromatography-mass spectrometry) were used to analyze the metabolites. Multiple aliquots were simultaneously, and in parallel, analyzed, and, after appropriate quality control (QC), the information derived from each analysis was recombined. Every sample was characterized according to several thousand characteristics, which ultimately amount to several hundred chemical species. The techniques used were able to identify novel and chemically unnamed compounds.
B. Statistical Analysis
The data was analyzed using T-tests to identify molecules (either known, named metabolites or unnamed metabolites) present at differential levels in a definable population or subpopulation (e.g., biomarkers for prostate cancer biological samples compared to control biological samples or compared to patients in remission from prostate cancer) useful for distinguishing between the definable populations (e.g., prostate cancer and control, low grade prostate cancer and high grade prostate cancer). Other molecules (either known, named metabolites or unnamed metabolites) in the definable population or subpopulation were also identified.
Data was also analyzed using Random Forest Analysis. Random forests give an estimate of how well individuals in a new data set can be classified into existing groups. Random forest analysis creates a set of classification trees based on continual sampling of the experimental units and compounds. Then each observation is classified based on the majority votes from all the classification trees. In statistics, a classification tree classifies the observations into groups based on combinations of the variables (in this instance variables are metabolites or compounds). There are many variations on the algorithms used to create trees. A tree algorithm searches for the metabolite (compound) that provides the largest split between the two groups. This produces nodes. Then at each node, the metabolite that provides the best split is used and so on. If the node cannot be improved on, then it stops at that node and any observation in that node is classified as the majority group.
Random forests classify based on a large number (e.g. thousands) of trees. A subset of compounds and a subset of observations are used to create each tree. The observations used to create the tree are called the in-bag samples, and the remaining samples are called the out-of-bag samples. The classification tree is created from the in-bag samples, and the out-of-bag samples are predicted from this tree. To get the final classification for an observation, the “votes” for each group are counted based on the times it was an out-of-bag sample. For example, suppose observation 1 was classified as a “Control” by 2,000 trees, but classified as “Disease” by 3,000 trees. Using “majority wins” as the criterion, this sample is classified as “Disease.”
The results of the random forest are summarized in a confusion matrix. The rows correspond to the true grouping, and the columns correspond to the classification from the random forest. Thus, the diagonal elements indicate the correct classifications. A 50% error would occur by random chance for 2 groups, 66.67% error for three groups by random chance, etc. The “Out-of-Bag” (OOB) Error rate gives an estimate of how accurately new observations can be predicted using the random forest model (e.g., whether a sample is from a diseased subject or a control subject).
It is also of interest to see which variables are more “important” in the final classifications. The “importance plot” shows the top compounds ranked in terms of their importance. There are different criteria for ranking the importance, but the general idea is that removing an important variable will cause a greater decrease in accuracy than a variable that is less important.
C. Biomarker Identification
Various peaks identified in the analyses (e.g. GC-MS, LC-MS, MS-MS), including those identified as statistically significant, were subjected to a mass spectrometry based chemical identification process.
Example 1
Tissue
Biomarkers were discovered by (1) analyzing tissue samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
The tissue samples used for the analysis were 16 control tissues that were cancer free tissues derived from sections of prostate tissue not containing cancer cells (i.e. from cancerous prostate glands and that were determined to be free of cancerous cells), 12 prostate tissue samples from localized prostate cancer tumors (i.e. lower grade prostate cancer) and 14 prostate tissue samples from distal metastatic prostate cancer tumors (i.e. high grade prostate cancer). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate Cancer vs. Control, Metastatic/High Grade Prostate Cancer vs. Control, Metastatic/High Grade Prostate Cancer vs. Lower Grade Prostate Cancer).
Biomarkers:
As listed below in Table 1, biomarkers were discovered that were differentially present between tissue samples from lower grade, localized prostate cancer tumors and Control prostate tissue that was determined to be free of cancerous cells (i.e. sections of prostate tissue not containing cancerous cells from cancerous prostate glands removed from the patient). Table 2 lists biomarkers that were discovered that were differentially present between tissue from prostate tumor samples from subjects with metastatic prostate cancer (i.e. high grade prostate cancer) and Control prostate tissue. Table 3 lists biomarkers that were discovered that were differentially present between tissue samples from prostate tumor samples from subjects with metastatic prostate cancer (i.e. high grade prostate cancer) and tissue samples from lower grade, localized prostate cancer tumors.
Tables 1-3 include, for each listed biomarker, the p-value and the q-value determined in the statistical analysis of the data concerning the biomarkers and an indication of the percentage difference in the lower grade prostate cancer (PCA) mean level as compared to the control mean level (Table 1), the high grade prostate cancer mean level as compared to the control mean level (Table 2), and the high grade prostate cancer mean level as compared to the lower grade prostate cancer mean level (Table 3). The term “Isobar” as used in the tables indicates the compounds that could not be distinguished from each other on the analytical platform used in the analysis (i.e., the compounds in an isobar elute at nearly the same time and have similar (and sometimes exactly the same) quant ions, and thus cannot be distinguished). Library indicates the chemical library that was used to identify the compounds. The number 50 refer to the GC library and the number 61 refers to the LC library.







TABLE 1







Prostate Cancer Biomarkers from subjects with Lower Grade Prostate


Cancer compared to Control subjects.















%



Li-


Change


COMPOUND
brary
p-value
q-value
in PCA














Metabolite - 3139
61
<0.0001
0.0019
147%


Metabolite - 1114
61
<0.0001
0.0053
55%


uridine
61
1.00E−04
0.0064
71%


Metabolite - 3778
61
1.00E−04
0.0064
−67%


dethiobiotin
50
1.00E−04
0.0064
62%


Metabolite - 3094
50
1.00E−04
0.0075
62%


N-acetyl-D-galactosamine
50
2.00E−04
0.0092
214%


4-hydroxy-2-quinolinecarboxylic
61
3.00E−04
0.0092
110%


acid


Metabolite - 4019
50
3.00E−04
0.0092
104%


Metabolite - 2688
61
3.00E−04
0.0092
20%


proline
50
3.00E−04
0.0092
59%


Metabolite - 1111-possible-
61
3.00E−04
0.0092
92%


methylnitronitrosoguanidine-or-


ethyl-thiocarbamoylacetate


glutamic acid
50
4.00E−04
0.0095
83%


3-hydroxy-3-methylglutarate
50
5.00E−04
0.0107
82%


Metabolite - 3810
61
6.00E−04
0.0119
−45%


Metabolite - 1576
61
6.00E−04
0.0119
116%


Metabolite - 4637
50
7.00E−04
0.0134
55%


Metabolite - 1595-possible-
61
7.00E−04
0.0134
−58%


glutathione-metabolite


glycine
50
8.00E−04
0.0142
67%


leucine
50
9.00E−04
0.0145
61%


threonine
50
9.00E−04
0.0145
51%


histidine
50
0.001
0.0151
58%


anthranilic acid
50
0.0012
0.0167
53%


asparagine
50
0.0012
0.0167
81%


L-allo-threonine
50
0.0014
0.0177
48%


n-hexadecanoic acid
50
0.0014
0.0177
36%


1-7-dihydro-6h-purin-6-one
61
0.0016
0.0193
43%


N-acetyl-D-glucosamine
50
0.0016
0.0193
125%


DL-homocysteine
61
0.0019
0.021
118%


sn-Glycerol-3-phosphate
50
0.0019
0.021
98%


Isobar-2-includes-3-amino-
61
0.0021
0.0219
58%


isobutyrate-2-amino-butyrate-4-


aminobutanoic acid-


dimethylglycine-choline-


3-phospho-l-serine
61
0.0023
0.0228
18%


Isobar-27-includes-L-
61
0.0024
0.0228
90%


kynurenine-alpha-2-diamino-


gamma-oxobenzenebutanoic


acid


Metabolite - 4051
50
0.0024
0.0228
108%


alpha-amino-adipate
50
0.0026
0.0228
99%


Metabolite - 4117-possible-
61
0.0026
0.0228
163%


propranolol-or-2-heptyl-3-


hydroxy-quinolone


cholesterol
50
0.0027
0.0228
46%


Metabolite - 5128
61
0.0027
0.0228
−85%


Isobar-6-includes-valine-betaine
61
0.0029
0.0228
36%


Metabolite - 4616
61
0.0029
0.0228
269%


Metabolite - 4015
50
0.0029
0.0228
102%


Metabolite - 2973
50
0.0029
0.0228
−25%


valine
50
0.003
0.0233
38%


malic acid
50
0.0032
0.0237
62%


Metabolite - 1211
61
0.0033
0.0241
−52%


Isobar-22-includes-glutamic
61
0.0037
0.0263
44%


acid-O-acetyl-L-serine


tetradecanoic acid
50
0.0038
0.0263
59%


phosphate
50
0.0039
0.0265
68%


possible-ISOBAR-DL-aspartic
50
0.004
0.0267
71%


acid-


Metabolite - 2466
61
0.0041
0.0271
99%


Metabolite - 2548
61
0.0044
0.0283
−32%


Metabolite - 3848
61
0.0045
0.0283
117%


Metabolite - 2109
61
0.0046
0.0283
120%


tryptophan
61
0.0046
0.0283
38%


2-acetamido-1-amino-1-2-
50
0.0054
0.0324
134%


dideoxy-beta-D-glucopyranose


Metabolite - 3998
50
0.0057
0.0324
53%


5-oxoproline
50
0.0057
0.0324
48%


riboflavine
61
0.0058
0.0324
67%


phytonadione
50
0.0059
0.0324
45%


Metabolite - 2074
61
0.0059
0.0324
−42%


9-12-octadecadienoic acid-z-z-
50
0.0061
0.0328
74%


carnitine
61
0.0063
0.033
47%


Metabolite - 3370
61
0.0063
0.033
37%


uracil
50
0.0067
0.0343
129%


noradrenaline
50
0.0068
0.0344
50%


tyrosine
61
0.007
0.0348
41%


cysteine
50
0.0073
0.036
800%


25-hydroxycholesterol
50
0.0075
0.0364
18%


Metabolite - 4030-possible-
61
0.0076
0.0366
109%


glutethimide-or-securinine


N-acetylserotonin
50
0.008
0.0376
279%


Metabolite - 2108
61
0.0081
0.0376
78%


phenylalanine
61
0.0082
0.0376
36%


Isobar-3-includes-inositol-1-
61
0.0088
0.0395
63%


phosphate-mannose-6-


phosphate-glucose-6-


phosphate-D-mannose-1-


phosphate-alpha-D-glucose-1-


phosphate-alpha-D-galactose-1-


phosphate


Metabolite - 1713
61
0.0089
0.0395
82%


Metabolite - 1977
61
0.0094
0.0412
218%


octadecanoic acid
50
0.0099
0.0429
25%


3-nitro-L-tyrosine
50
0.0101
0.0434
82%


Metabolite - 2064
61
0.0112
0.0472
44%


Metabolite - 2389
61
0.0123
0.051
36%


Metabolite - 4617
61
0.0124
0.051
53%


orotidine-5-phosphate
61
0.013
0.0528
125%


serine
50
0.0135
0.0542
40%


spermine
50
0.0143
0.0565
−78%


Metabolite - 2041
61
0.0145
0.0565
157%


Metabolite - 1465
61
0.0146
0.0565
174%


N-5-aminocarbonyl-L-ornithine
50
0.0158
0.0607
136%


2-deoxy-D-ribose
61
0.0164
0.062
44%


heptadecanoic acid
50
0.0168
0.0622
76%


Metabolite - 3165
61
0.0172
0.0622
26%


methionine
61
0.0173
0.0622
43%


S-adenosyl-l-homocysteine
61
0.0173
0.0622
41%


Isobar-24-includes-L-arabitol-
61
0.0174
0.0622
46%


adonitol


glycerol
50
0.0175
0.0622
51%


Metabolite - 2690
61
0.019
0.0662
147%


Metabolite - 3176-possible-
61
0.0191
0.0662
−22%


creatine


Metabolite - 4632
50
0.0197
0.0675
44%


aspartate
61
0.0207
0.0695
54%


Metabolite - 3027
50
0.0207
0.0695
108%


mannose-6-phosphate
50
0.022
0.0734
179%


Metabolite - 5215
50
0.0225
0.0742
−27%


Metabolite - 2055
61
0.0229
0.0744
−35%


uridine-5-monophosphate
61
0.023
0.0744
−38%


Metabolite - 4046
50
0.0249
0.0797
305%


Metabolite - 4355
50
0.0256
0.0797
36%


Metabolite - 4058
50
0.0256
0.0797
104%


Carnosine
61
0.0256
0.0797
−45%


Metabolite - 1070
61
0.0263
0.0811
109%


Metabolite - 5228
50
0.0279
0.0852
52%


Metabolite - 2753
61
0.0286
0.0861
224%


Metabolite - 4116
61
0.0289
0.0861
34%


Metabolite - 2272
61
0.0292
0.0861
152%


Metabolite - 4027
50
0.0294
0.0861
145%


xanthine
61
0.0298
0.0861
172%


Metabolite - 2924
50
0.0298
0.0861
51%


N-N-dimethylarginine
61
0.0318
0.0911
224%


Metabolite - 4017
50
0.0322
0.0915
52%


glutamine
50
0.0333
0.0924
39%


isoleucine
50
0.0335
0.0924
26%


Metabolite - 1498
61
0.0336
0.0924
48%


adenine
50
0.0336
0.0924
65%


Metabolite - 2005
61
0.0345
0.0941
45%


sarcosine
50
0.0354
0.0958
150%


Metabolite - 3498
61
0.0366
0.098
55%


Metabolite - 5210
50
0.0396
0.1052
−23%


arginino-succinate
61
0.043
0.1132
93%


Putrescine
50
0.0432
0.1132
−82%


Metabolite - 1104
61
0.0441
0.1144
−35%


taurine
61
0.0455
0.1171
−21%


Metabolite - 1597
61
0.0461
0.1178
29%


Metabolite - 4043
50
0.0469
0.119
33%


Metabolite - 3183-possible-
61
0.0475
0.1195
107%


gamma-L-glutamyl-L-


phenylalanine-or-aspartame


N-6-trimethyl-l-lysine
61
0.0486
0.1215
35%


Metabolite - 2250
61
0.0508
0.1261
71%


creatinine
61
0.0514
0.1261
−25%


melatonin
50
0.0516
0.1261
111%


Metabolite - 2105
61
0.0541
0.1311
100%


2-deoxyuridine-5-triphosphate
61
0.0571
0.1375
−41%


tyramine
50
0.0591
0.1404
32%


inositol-1-phosphate
50
0.0592
0.1404
40%


4-methyl-2-oxopentanoate
61
0.0597
0.1405
162%


Metabolite - 5186
61
0.0601
0.1406
600%


fumaric acid
50
0.0638
0.1482
82%


2-deoxyuridine
61
0.0676
0.156
74%


Metabolite - 1085-possible-
61
0.0688
0.1576
45%


isolobinine-or-4-aminoestra-1-3-


5-10-triene-3-17beta-diol


Metabolite - 4868-possible-
61
0.0703
0.1598
114%


Bradykinin


Metabolite - 2846
61
0.0753
0.1701
141%


arachidonic acid
50
0.0765
0.1705
52%


Metabolite - 1831-possible-Cl-
61
0.0769
0.1705
30%


adduct-of-citrulline


Metabolite - 3099
50
0.0771
0.1705
43%


trans-4-hydroxyproline
50
0.0776
0.1705
63%


Metabolite - 3783
61
0.0782
0.1708
−39%


L-alpha-
61
0.0793
0.172
58%


glycerophosphorylcholine


glycerate
61
0.0798
0.172
42%


cytidine
61
0.0819
0.1741
101%


Isobar-40-includes-
61
0.0825
0.1741
−41%


Maltotetraose-stachyose


Metabolite - 1679
61
0.0831
0.1741
347%


Metabolite - 4032
50
0.0836
0.1741
108%


Metabolite - 3752
61
0.0841
0.1741
756%


Isobar-32-includes-N-acetyl-D-
61
0.0847
0.1741
34%


glucosamine-N-acetyl-D-


mannosamine


pantothenic acid
61
0.0849
0.1741
40%


glyceric acid
50
0.085
0.1741
27%


xylitol
50
0.0907
0.1831
65%


Metabolite - 2075
61
0.0915
0.1831
148%


Metabolite - 3430
61
0.0916
0.1831
63%


Metabolite - 3668
61
0.0917
0.1831
−47%


5-6-dihydrouracil
61
0.0928
0.1831
94%


Metabolite - 3138
61
0.0933
0.1831
62%


Metabolite - 2056
61
0.0933
0.1831
−20%


Metabolite - 4362
50
0.0944
0.1834
−41%


Metabolite - 4514
50
0.095
0.1834
−19%


Metabolite - 2607
61
0.0959
0.1834
−45%


Isobar-21-includes-gamma-
61
0.096
0.1834
70%


aminobutyryl-L-histidine-L-


anserine


Isobar-5-includes-asparagine-
61
0.0963
0.1834
57%


ornithine


Metabolite - 3957
61
0.0968
0.1834
43%


Isobar-30-includes-
61
0.0993
0.1867
−35%


maltotetraose-stachyose


D-sorbitol-6-phosphate
50
0.0996
0.1867
53%


Metabolite - 2981
50
0.1017
0.1894
17%


ribulose-5-phosphate
50
0.1041
0.1929
−25%


Metabolite - 3123
61
0.1082
0.1987
−42%


Isobar-18-includes-D-fructose-1-
61
0.1085
0.1987
67%


phosphate-beta-D-fructose-6-


phosphate


Metabolite - 1593
61
0.111
0.2022
−44%


uric acid
61
0.1119
0.2027
−19%


Metabolite - 3178
61
0.1128
0.2027
−30%


Metabolite - 1455
61
0.1131
0.2027
−81%


Metabolite - 1286
61
0.1145
0.204
−16%


Isobar-1-includes-mannose-
61
0.1166
0.2068
−35%


fructose-glucose-galactose-


alpha-L-sorbopyranose-Inositol-


D-allose


o-phosphoethanolamine
50
0.1196
0.211
44%


Metabolite - 1608
61
0.1206
0.2115
−59%


Metabolite - 3539
61
0.1217
0.2123
−57%


Metabolite - 4593
50
0.1257
0.217
37%


palmitoleic acid
50
0.1257
0.217
78%


Metabolite - 3896
61
0.1274
0.2176
65%


1-methyladenosine
61
0.1274
0.2176
100%


Metabolite - 1203-possible-
61
0.1333
0.2253
86%


acetylbrowniine-tricornine-


germine-or-veracevine


Metabolite - 3771
61
0.1338
0.2253
−18%


pyridoxamine-phosphate
61
0.1341
0.2253
−33%


Metabolite - 2212
61
0.135
0.2253
320%


Spermidine
50
0.1367
0.2253
−51%


Metabolite - 3992-
61
0.1375
0.2253
14%


Metabolite - 3044
61
0.1385
0.2253
30%


3-methyl-L-histidine
61
0.1389
0.2253
21%


Metabolite - 2546
61
0.1393
0.2253
−36%


fructose
50
0.1396
0.2253
−47%


Metabolite - 3816
61
0.1397
0.2253
−43%


Metabolite - 2255
61
0.1406
0.2253
44%


Metabolite - 3073
50
0.1407
0.2253
−39%


succinate
50
0.1456
0.2314
−54%


Metabolite - 2292
61
0.1459
0.2314
−35%


glutathione-reduced
61
0.1467
0.2314
−43%


alanine
50
0.1494
0.2346
21%


Metabolite - 4053
50
0.1527
0.2387
26%


Metabolite - 4567
61
0.1555
0.2419
−37%


Metabolite - 3832-possible-
61
0.1614
0.2499
−30%


phenol-sulfate


Metabolite - 5189
61
0.1668
0.2571
263%


saccharopine
61
0.1679
0.2575
23%


Metabolite - 1216
61
0.1699
0.2577
53%


Metabolite - 5227
50
0.1704
0.2577
45%


citric acid
50
0.1708
0.2577
−37%


catechol
61
0.1712
0.2577
77%


Metabolite - 4615
61
0.1733
0.2594
−13%


Metabolite - 3808
61
0.1747
0.2594
−20%


Metabolite - 1609
61
0.1753
0.2594
−35%


D-allose
50
0.1754
0.2594
−37%


elaidic acid
50
0.1821
0.2681
84%


Metabolite - 2129
61
0.1835
0.269
110%


Metabolite - 2185
61
0.1864
0.2706
35%


azelaic acid
61
0.1875
0.2706
63%


Metabolite - 1088
61
0.1879
0.2706
81%


Metabolite - 5232
50
0.1879
0.2706
109%


Isobar-17-includes-arginine-N-
61
0.1887
0.2706
25%


alpha-acetyl-ornithine


hypotaurine
50
0.1917
0.2736
36%


Metabolite - 4150
50
0.1936
0.2744
−36%


Metabolite - 2111
61
0.1939
0.2744
33%


Metabolite - 1457
61
0.1957
0.2758
−35%


DL-cystathionine
50
0.1983
0.2783
22%


Metabolite - 5147
61
0.2019
0.2822
243%


Metabolite - 3476
61
0.2033
0.2828
−23%


benzoic acid
50
0.2043
0.2831
−14%


Metabolite - 5109
61
0.2069
0.2843
89%


Metabolite - 3102
50
0.2082
0.2843
25%


Metabolite - 3974
61
0.2083
0.2843
38%


Metabolite - 1351
61
0.2086
0.2843
19%


mannose
50
0.2108
0.2858
−32%


quinolinic acid
61
0.2114
0.2858
42%


gamma-L-glutamyl-L-glutamine
61
0.2161
0.2896
−28%


Metabolite - 1186
61
0.2164
0.2896
−54%


Metabolite - 2766
61
0.2183
0.2896
−34%


phosphoenolpyruvate
50
0.2184
0.2896
105%


Metabolite - 4080
50
0.2187
0.2896
71%


Metabolite - 2139
61
0.221
0.2915
41%


Metabolite - 2900-
61
0.222
0.2915
24%


Metabolite - 2388
61
0.2232
0.2915
24%


2-deoxy-D-glucose
50
0.2236
0.2915
−30%


5-hydroxyindoleacetate
50
0.2255
0.2928
210%


Metabolite - 4869
61
0.2292
0.2964
−38%


Metabolite - 2774
61
0.2377
0.306
47%


Metabolite - 2232
61
0.2385
0.306
−36%


3-methoxy-L-tyrosine
50
0.2401
0.3069
−29%


inositol
50
0.2414
0.3071
−29%


glucono-gamma-lactone
50
0.2434
0.3071
−31%


Metabolite - 4133
50
0.2441
0.3071
34%


Metabolite - 4014
50
0.2444
0.3071
−17%


galactose
50
0.2449
0.3071
30%


Metabolite - 3813
61
0.248
0.3097
115%


Metabolite - 1980
61
0.2537
0.3151
119%


Metabolite - 5108
61
0.2542
0.3151
72%


Metabolite - 2703
61
0.2562
0.3165
31%


Metabolite - 5110
61
0.2632
0.3239
63%


Metabolite - 5207
50
0.2649
0.3247
13%


Metabolite - 2027
61
0.2671
0.3262
47%


2-keto-L-gulonic acid
50
0.2795
0.34
12%


Metabolite - 3064
61
0.2832
0.3434
50%


glucose-6-phosphate
50
0.2849
0.3439
−28%


Metabolite - 5166
61
0.2857
0.3439
49%


3-amino-isobutyrate
50
0.2892
0.3457
−27%


dulcitol
50
0.2894
0.3457
−27%


Metabolite - 3034
50
0.2933
0.349
22%


Metabolite - 4667
61
0.2942
0.349
18%


Metabolite - 2806
61
0.2996
0.3541
−12%


Metabolite - 5089
61
0.3011
0.3541
−65%


4-hydroxyphenylpyruvate
61
0.3034
0.3541
−17%


Metabolite - 4075
50
0.3039
0.3541
36%


Metabolite - 4235
61
0.3039
0.3541
−67%


glutarate
61
0.3122
0.358
47%


beta-nicotinamide-adenine-
61
0.3134
0.358
445%


dinucleotide


Metabolite - 1327-possible-
61
0.3175
0.358
30%


bilirubin


guanine
50
0.3177
0.358
26%


Metabolite - 1323-possible-4-
61
0.3181
0.358
−31%


sulfobenzyl-alcohol


Metabolite - 3708
61
0.3196
0.358
−10%


Metabolite - 4706
61
0.3202
0.358
42%


Metabolite - 3545
61
0.3204
0.358
76%


Metabolite - 3132
61
0.3217
0.358
23%


niacinamide
61
0.3243
0.358
12%


Metabolite - 3514-retired-
61
0.3248
0.358
−89%


topiramate


Metabolite - 5167
61
0.3248
0.358
43%


Metabolite - 5170
61
0.3251
0.358
854%


Metabolite - 3951
61
0.3267
0.358
13%


Metabolite - 2768
61
0.3321
0.358
798%


allantoin
61
0.3332
0.358
−15%


Metabolite - 2347
61
0.3332
0.358
−16%


Metabolite - 3436
61
0.3332
0.358
−21%


Metabolite - 5087
61
0.3338
0.358
−53%


Metabolite - 3576
61
0.3374
0.358
23%


Metabolite - 3694
61
0.3383
0.358
36%


Metabolite - 3522
61
0.3398
0.358
−85%


Metabolite - 2406
61
0.3409
0.358
31%


Metabolite - 3364
61
0.3409
0.358
12%


Metabolite - 3997
61
0.3409
0.358
43%


Metabolite - 4018
61
0.3409
0.358
38%


suberic acid
61
0.3409
0.358
15%


Metabolite - 3022
50
0.3409
0.358
8%


Metabolite - 1329
61
0.3409
0.358
10%


Metabolite - 3756
61
0.3409
0.358
25%


Metabolite - 5086
61
0.3409
0.358
−41%


Metabolite - 1911
61
0.3431
0.3582
64%


gamma-glu-cys
61
0.3432
0.3582
60%


N-acetylneuraminate
61
0.3469
0.3609
−14%


Metabolite - 2691
61
0.3544
0.3669
33%


Metabolite - 3531
61
0.3572
0.3669
−70%


Metabolite - 3180
61
0.3575
0.3669
46%


L-homoserine-lactone
61
0.3583
0.3669
12%


Metabolite - 1974
61
0.3584
0.3669
−18%


Metabolite - 2141
61
0.3594
0.3669
29%


Metabolite - 1333
61
0.3625
0.3684
28%


GABA
50
0.3631
0.3684
−20%


adenosine
61
0.3676
0.3719
−18%


Metabolite - 5226
50
0.3709
0.3741
33%


Metabolite - 2036
61
0.3733
0.3748
−38%


Metabolite - 1616
61
0.3739
0.3748
76%


Metabolite - 3833
61
0.3752
0.375
20%


Metabolite - 2348
61
0.3836
0.3813
69%


S-5-adenosyl-L-methionine
61
0.3839
0.3813
30%


Metabolite - 4331
61
0.3854
0.3817
26%


Metabolite - 3475
61
0.3873
0.3824
−19%


n-dodecanoate
50
0.3957
0.3895
15%


Metabolite - 3952
61
0.399
0.3914
−14%


Metabolite - 3837
61
0.3999
0.3914
−33%


Metabolite - 1819
61
0.4015
0.3917
−15%


Metabolite - 2853
61
0.4036
0.3926
−20%


Metabolite - 3517
61
0.4048
0.3926
−34%


Metabolite - 3526
61
0.4155
0.4018
−23%


Metabolite - 2711
61
0.4182
0.4029
11%


5-s-methyl-5-thioadenosine
61
0.419
0.4029
33%


xanthosine
50
0.4265
0.4088
−18%


Metabolite - 5107
61
0.4345
0.4153
36%


Metabolite - 1248-possible-
61
0.4438
0.421
22%


avermectin-aglycone


ornithine
50
0.4438
0.421
19%


Metabolite - 3984
61
0.4443
0.421
58%


Metabolite - 3215
61
0.4466
0.4219
−18%


Metabolite - 2181
61
0.45
0.423
23%


Metabolite - 1392
61
0.4505
0.423
−49%


Metabolite - 4512
50
0.4516
0.423
34%


Metabolite - 5209
50
0.4539
0.4241
−16%


Metabolite - 2198
61
0.4573
0.4251
−19%


Metabolite - 4931
61
0.4578
0.4251
11%


Metabolite - 3604
61
0.4589
0.4251
30%


maltose
50
0.4614
0.4253
−13%


Metabolite - 1330
61
0.4623
0.4253
−50%


Metabolite - 1843
61
0.4644
0.4253
35%


Metabolite - 5214
50
0.4665
0.4253
−19%


Metabolite - 3056
61
0.467
0.4253
−23%


Metabolite - 4084
50
0.468
0.4253
−5%


Metabolite - 2567
61
0.4682
0.4253
15%


Metabolite - 3893
61
0.4774
0.4323
−14%


Metabolite - 3543
61
0.4785
0.4323
−47%


Metabolite - 4503
50
0.4815
0.4338
21%


Isobar-31-includes-maltotriose-
61
0.4912
0.4406
−14%


melezitose


histamine
61
0.4917
0.4406
−13%


D-ribose
50
0.4931
0.4407
−17%


Metabolite - 3390
61
0.4987
0.4445
−4%


6-phosphogluconic acid
61
0.5166
0.4592
−7%


Metabolite - 2319
61
0.5186
0.4597
24%


lactate
50
0.523
0.4624
8%


Metabolite - 4096-gamma-glu-
61
0.5325
0.4695
−7%


gly-leu-


Metabolite - 4518
50
0.5347
0.4701
22%


Metabolite - 1129
61
0.536
0.4701
23%


Metabolite - 3003
50
0.5401
0.4724
15%


Metabolite - 5213
50
0.5456
0.476
−11%


Metabolite - 1069-possible-
61
0.549
0.4771
25%


dehydroepiandrosterone-sulfate-


Metabolite - 1575
61
0.5511
0.4771
−16%


3-hydroxybutanoic acid
50
0.5512
0.4771
−22%


Metabolite - 4238
61
0.553
0.4773
14%


pyrophosphate
50
0.5551
0.4779
20%


Metabolite - 2867
61
0.5592
0.4788
25%


Metabolite - 1718
61
0.5602
0.4788
20%


arabinose
50
0.5604
0.4788
−14%


Metabolite - 3401
61
0.5676
0.4836
−18%


beta-alanine
50
0.5697
0.4842
−12%


Metabolite - 2897
61
0.5738
0.4856
−13%


Metabolite - 1394-possible-
61
0.5743
0.4856
23%


Losartan


Metabolite - 4428
61
0.5759
0.4857
21%


Metabolite - 2099
61
0.5866
0.4924
26%


Metabolite - 3220
61
0.5868
0.4924
10%


Metabolite - 3317
61
0.5908
0.4932
19%


biliverdin
61
0.5908
0.4932
−12%


Metabolite - 3002
50
0.5925
0.4934
6%


Metabolite - 3955
61
0.5991
0.4976
−4%


Metabolite - 3020
50
0.6009
0.4979
12%


Metabolite - 3189
61
0.6061
0.5009
−23%


Metabolite - 1970
61
0.6121
0.5046
19%


Metabolite - 1963
61
0.6203
0.5078
−9%


Metabolite - 1113-possible-
61
0.6216
0.5078
−6%


acetylcarnitine-or-isopentyl-


adenine


Metabolite - 3016
50
0.6232
0.5078
−12%


caffeine
61
0.6241
0.5078
22%


ethylmalonic acid
61
0.6247
0.5078
38%


cystine
50
0.6255
0.5078
8%


Metabolite - 2558
61
0.6268
0.5078
−21%


uridine-5-diphosphoglucose
50
0.629
0.5084
8%


3-methyl-2-oxovaleric acid
61
0.634
0.5112
26%


dihydroxyacetone-phosphate
61
0.6396
0.5144
11%


Metabolite - 4497
50
0.6462
0.5184
−12%


Metabolite - 2313
61
0.649
0.5184
7%


Metabolite - 3085
50
0.6493
0.5184
−5%


Metabolite - 3996
50
0.6552
0.521
−9%


L-histidinol
61
0.6557
0.521
−9%


Metabolite - 1573
61
0.6598
0.5231
−9%


Metabolite - 2407
61
0.6624
0.5238
−18%


Metabolite - 5126
61
0.665
0.5246
11%


Metabolite - 4448
61
0.6685
0.5261
−8%


alpha-D-ribose-5-phosphate
50
0.6795
0.5319
9%


cytidine-5-monophosphate
61
0.6818
0.5319
11%


Metabolite - 1979-Cl-adduct-of-
61
0.6823
0.5319
5%


C6H10O5


Metabolite - 2-Aminoethyl-
61
0.6831
0.5319
4%


phosphonate


sorbitol
50
0.6839
0.5319
−21%


Metabolite - 2368
61
0.6862
0.5324
56%


Metabolite - 1961-retired-
61
0.7054
0.5461
45%


glycocholic acid


Metabolite - 4523
50
0.7076
0.5464
7%


alpha-4-
50
0.7136
0.5498
20%


dihydroxybenzenepropanoic


acid


Metabolite - 1342-possible-
61
0.728
0.5591
−15%


phenylacetylglutamine


Metabolite - 4020
50
0.7305
0.5591
9%


Metabolite - 3554
61
0.7316
0.5591
14%


Metabolite - 2174
61
0.7325
0.5591
9%


Metabolite - 4002
50
0.7391
0.5629
8%


DL-pipecolic acid
61
0.7474
0.5674
−8%


Metabolite - 2824
61
0.7484
0.5674
14%


Metabolite - 3807
61
0.7516
0.5685
−4%


Metabolite - 3129
61
0.7585
0.5724
−3%


Metabolite - 2194
61
0.7641
0.5735
−9%


ascorbic acid
50
0.7647
0.5735
−10%


biotin
61
0.7657
0.5735
−9%


Metabolite - 1975
61
0.7669
0.5735
−8%


Metabolite - 1349
61
0.7721
0.576
−6%


Metabolite - 2072
61
0.7799
0.5792
−9%


Metabolite - 1142-possible-5-
61
0.7817
0.5793
4%


hydroxypentanoate-or-beta-


hydroxyisovaleric acid


Metabolite - 4806
50
0.7875
0.581
3%


Metabolite - 4796
50
0.7882
0.581
−9%


4-Guanidinobutanoic acid
61
0.7894
0.581
6%


Metabolite - 3489
61
0.7984
0.5855
−7%


Metabolite - 1116
61
0.799
0.5855
−5%


Metabolite - 2827
61
0.8024
0.5867
13%


Metabolite - 3772
61
0.814
0.5923
4%


Metabolite - 2143
61
0.8147
0.5923
−12%


Metabolite - 3960
61
0.8168
0.5923
2%


Metabolite - 3040
50
0.8172
0.5923
3%


Metabolite - 3994
61
0.8202
0.5931
−8%


Metabolite - 2180
61
0.8237
0.5944
−7%


Metabolite - 2118
61
0.8311
0.5974
−3%


Metabolite - 4787
61
0.8315
0.5974
15%


Metabolite - 4516
50
0.8341
0.5979
−6%


Metabolite - 4168
61
0.8386
0.598
4%


uridine-5-diphosphoglucuronic
50
0.841
0.598
7%


acid


Metabolite - 4134
50
0.8433
0.598
3%


Metabolite - 4271
50
0.8442
0.598
−17%


Metabolite - 2121
61
0.8444
0.598
8%


Metabolite - 4013
61
0.8451
0.598
5%


urea
50
0.8512
0.6007
−2%


Metabolite - 4272
50
0.8534
0.6007
−4%


Metabolite - 1653
61
0.855
0.6007
6%


Metabolite - 1183
61
0.8561
0.6007
9%


Metabolite - 5229
50
0.8587
0.6012
3%


glucarate
50
0.8678
0.6063
14%


Metabolite - 1187
61
0.8864
0.6163
5%


beta-D-lactose
50
0.8875
0.6163
3%


Metabolite - 2279
61
0.8877
0.6163
−4%


Metabolite - 5212
50
0.8914
0.617
3%


alpha-L-sorbopyranose
50
0.8925
0.617
−3%


Metabolite - 4354
50
0.9014
0.6219
−2%


Metabolite - 3014
50
0.9104
0.6256
1%


Metabolite - 3534
61
0.9131
0.6256
−5%


Metabolite - 3966
61
0.9137
0.6256
−4%


Metabolite - 1497
61
0.9149
0.6256
−2%


Metabolite - 3379
61
0.9178
0.6256
−2%


Metabolite - 1288
61
0.9188
0.6256
3%


Metabolite - 2237
61
0.9222
0.6256
4%


Metabolite - 3755
61
0.9248
0.6256
2%


Metabolite - 3980
61
0.9253
0.6256
−3%


picolinic acid
61
0.9259
0.6256
3%


Metabolite - 2821
61
0.9284
0.6261
−2%


L-kynurenine
50
0.9317
0.627
−3%


inosine
61
0.9399
0.6272
−1%


Metabolite - 2724
61
0.9415
0.6272
−1%


Isobar-19-includes-D-saccharic
61
0.9431
0.6272
1%


acid-2-deoxy-D-galactose-2-


deoxy-D-glucose-L-fucose-L-


rhamnose


Metabolite - 4510
50
0.9434
0.6272
−1%


alpha-keto-glutarate
61
0.9448
0.6272
−6%


3-methylglutaric acid
61
0.9453
0.6272
0%


Metabolite - 3051
61
0.9454
0.6272
2%


Metabolite - 3484
61
0.9472
0.6272
−3%


Metabolite - 1303
61
0.9513
0.6276
−2%


Metabolite - 3074
50
0.9517
0.6276
3%


guanosine
61
0.9553
0.6288
0%


hippuric acid
61
0.9589
0.6288
2%


Metabolite - 5211
50
0.9591
0.6288
3%


Metabolite - 5187
61
0.9644
0.6297
1%


Metabolite - 1496
61
0.9648
0.6297
0%


Metabolite - 4550
61
0.9663
0.6297
−2%


Metabolite - 3365
61
0.97
0.6309
1%


Metabolite - 4611
50
0.9734
0.6318
0%


Isobar-4-includes-Gluconic acid-
61
0.9753
0.6318
1%


DL-arabinose-D-ribose-L-xylose-


DL-lyxose-D-xylulose


1-methyladenine
50
0.979
0.633
2%


3-phospho-d-glycerate
61
0.9819
0.633
1%


Metabolite - 4365
50
0.9829
0.633
−1%


Metabolite - 4866
61
0.9912
0.6371
0%


Metabolite - 4003
61
0.9994
0.6412
0%
















TABLE 2







Prostate Cancer Biomarkers from subjects with Metastatic, High


Grade Prostate Cancer compared to Control subjects.















% Change


COMPOUND
Library
p-value
q-value
in PCA














inosine
61
<0.0001
<0.0001
−269%


Metabolite - 2-Aminoethyl-phosphonate
61
<0.0001
<0.0001
−437%


Metabolite - 1597
61
<0.0001
<0.0001
110%


Metabolite - 1498
61
<0.0001
<0.0001
188%


octadecanoic acid
50
<0.0001
<0.0001
136%


Metabolite - 3390
61
<0.0001
<0.0001
−330%


riboflavine
61
<0.0001
<0.0001
196%


leucine
50
<0.0001
<0.0001
216%


phosphate
50
<0.0001
<0.0001
150%


anthranilic acid
50
<0.0001
<0.0001
140%


glycerol
50
<0.0001
<0.0001
352%


Metabolite - 3808
61
<0.0001
<0.0001
−452%


valine
50
<0.0001
<0.0001
103%


Metabolite - 1595-possible-glutathione-
61
<0.0001
<0.0001
−695%


metabolite


n-hexadecanoic acid
50
<0.0001
<0.0001
365%


heptadecanoic acid
50
<0.0001
<0.0001
201%


Metabolite - 3998
50
<0.0001
<0.0001
101%


Metabolite - 1679
61
<0.0001
<0.0001
597%


phenylalanine
61
<0.0001
<0.0001
93%


Isobar-24-includes-L-arabitol-adonitol
61
<0.0001
<0.0001
313%


Metabolite - 2292
61
<0.0001
<0.0001
−644%


tryptophan
61
<0.0001
<0.0001
112%


Metabolite - 3893
61
<0.0001
<0.0001
−757%


xanthine
61
<0.0001
<0.0001
1072%


glycerate
61
<0.0001
<0.0001
375%


Metabolite - 3178
61
<0.0001
<0.0001
−1223%


ribulose-5-phosphate
50
<0.0001
<0.0001
−272%


noradrenaline
50
<0.0001
<0.0001
88%


Metabolite - 3085
50
<0.0001
<0.0001
−224%


Metabolite - 2272
61
<0.0001
<0.0001
594%


Metabolite - 4013
61
<0.0001
<0.0001
443%


taurine
61
<0.0001
<0.0001
−219%


uracil
50
<0.0001
<0.0001
933%


Metabolite - 3165
61
<0.0001
<0.0001
75%


Metabolite - 2973
50
<0.0001
<0.0001
−214%


histidine
50
<0.0001
<0.0001
120%


adenosine
61
<0.0001
1.00E−04
−276%


9-12-octadecadienoic acid-z-z-
50
<0.0001
1.00E−04
518%


isoleucine
50
<0.0001
1.00E−04
68%


Metabolite - 3772
61
<0.0001
1.00E−04
83%


DL-homocysteine
61
<0.0001
1.00E−04
216%


pantothenic acid
61
<0.0001
1.00E−04
164%


Metabolite - 3778
61
<0.0001
1.00E−04
−327%


Metabolite - 4611
50
<0.0001
1.00E−04
388%


Isobar-6-includes-valine-betaine
61
<0.0001
1.00E−04
78%


tetradecanoic acid
50
<0.0001
1.00E−04
810%


Metabolite - 3810
61
<0.0001
1.00E−04
−261%


proline
50
<0.0001
1.00E−04
209%


Metabolite - 1576
61
1.00E−04
1.00E−04
204%


Metabolite - 5210
50
1.00E−04
1.00E−04
−231%


4-hydroxyphenylpyruvate
61
1.00E−04
1.00E−04
−423%


Metabolite - 3102
50
1.00E−04
1.00E−04
918%


gamma-L-glutamyl-L-glutamine
61
1.00E−04
1.00E−04
−433%


Metabolite - 1977
61
1.00E−04
1.00E−04
382%


palmitoleic acid
50
1.00E−04
1.00E−04
1547%


n-dodecanoate
50
1.00E−04
1.00E−04
418%


Metabolite - 1114
61
1.00E−04
1.00E−04
106%


Metabolite - 4617
61
1.00E−04
1.00E−04
217%


Metabolite - 5107
61
1.00E−04
1.00E−04
268%


L-allo-threonine
50
1.00E−04
2.00E−04
86%


threonine
50
1.00E−04
2.00E−04
88%


Metabolite - 3138
61
1.00E−04
2.00E−04
268%


tyrosine
61
1.00E−04
2.00E−04
68%


Metabolite - 1349
61
1.00E−04
2.00E−04
−885%


arachidonic acid
50
1.00E−04
2.00E−04
164%


Metabolite - 4046
50
1.00E−04
2.00E−04
3090%


Metabolite - 4620
61
1.00E−04
2.00E−04
854%


Metabolite - 4075
50
1.00E−04
2.00E−04
971%


urea
50
2.00E−04
2.00E−04
234%


Metabolite - 2181
61
2.00E−04
2.00E−04
189%


Metabolite - 5209
50
2.00E−04
2.00E−04
−539%


Metabolite - 2108
61
2.00E−04
2.00E−04
155%


Metabolite - 1351
61
2.00E−04
2.00E−04
366%


glycine
50
2.00E−04
2.00E−04
101%


Metabolite - 3003
50
2.00E−04
2.00E−04
122%


Metabolite - 4134
50
2.00E−04
2.00E−04
458%


Metabolite - 1329
61
2.00E−04
2.00E−04
171%


Metabolite - 1394-possible-Losartan
61
2.00E−04
2.00E−04
158%


Metabolite - 3014
50
2.00E−04
2.00E−04
327%


Metabolite - 1116
61
3.00E−04
3.00E−04
446%


Metabolite - 5212
50
3.00E−04
3.00E−04
−488%


Metabolite - 1465
61
3.00E−04
3.00E−04
512%


Metabolite - 5228
50
3.00E−04
3.00E−04
86%


Isobar-2-includes-3-amino-isobutyrate-
61
3.00E−04
3.00E−04
249%


2-amino-butyrate-4-aminobutanoic acid-


dimethylglycine-choline-


glutathione-reduced
61
3.00E−04
3.00E−04
−819%


1-7-dihydro-6h-purin-6-one
61
3.00E−04
3.00E−04
63%


Metabolite - 2924
50
3.00E−04
3.00E−04
332%


methionine
61
3.00E−04
3.00E−04
68%


Metabolite - 4649
61
4.00E−04
3.00E−04
224%


fumaric acid
50
4.00E−04
3.00E−04
196%


Metabolite - 1593
61
4.00E−04
4.00E−04
−409%


inositol-1-phosphate
50
4.00E−04
4.00E−04
163%


Metabolite - 4051
50
4.00E−04
4.00E−04
663%


lactate
50
4.00E−04
4.00E−04
49%


Metabolite - 4117-possible-propranolol-
61
4.00E−04
4.00E−04
267%


or-2-heptyl-3-hydroxy-quinolone


N-N-dimethylarginine
61
4.00E−04
4.00E−04
267%


Metabolite - 3370
61
4.00E−04
4.00E−04
79%


citric acid
50
5.00E−04
4.00E−04
−1943%


glyceric acid
50
5.00E−04
4.00E−04
125%


Metabolite - 3215
61
5.00E−04
4.00E−04
110%


1-methyladenosine
61
6.00E−04
5.00E−04
620%


5-hydroxyindoleacetate
50
6.00E−04
5.00E−04
−319%


S-5-adenosyl-L-methionine
61
6.00E−04
5.00E−04
230%


catechol
61
7.00E−04
5.00E−04
595%


Metabolite - 5110
61
7.00E−04
5.00E−04
278%


Metabolite - 1069-possible-
61
7.00E−04
5.00E−04
−379%


dehydroepiandrosterone-sulfate-


Metabolite - 4593
50
7.00E−04
5.00E−04
113%


elaidic acid
50
7.00E−04
5.00E−04
526%


Metabolite - 3833
61
7.00E−04
6.00E−04
247%


Metabolite - 2711
61
8.00E−04
6.00E−04
84%


carnitine
61
8.00E−04
6.00E−04
155%


D-allose
50
8.00E−04
6.00E−04
−1265%


Metabolite - 3094
50
9.00E−04
6.00E−04
49%


Metabolite - 5108
61
9.00E−04
6.00E−04
237%


Metabolite - 3064
61
9.00E−04
6.00E−04
195%


L-alpha-glycerophosphorylcholine
61
9.00E−04
6.00E−04
361%


Metabolite - 5128
61
9.00E−04
6.00E−04
−2480%


Metabolite - 2567
61
9.00E−04
6.00E−04
132%


uric acid
61
9.00E−04
7.00E−04
142%


quinolinic acid
61
0.001
7.00E−04
173%


Metabolite - 4518
50
0.001
7.00E−04
618%


Metabolite - 4428
61
0.001
7.00E−04
210%


Metabolite - 5214
50
0.0011
7.00E−04
−421%


Metabolite - 3044
61
0.0011
7.00E−04
187%


Metabolite - 3816
61
0.0011
7.00E−04
−2267%


Metabolite - 1831-possible-Cl-adduct-
61
0.0011
7.00E−04
142%


of-citrulline


guanosine
61
0.0012
7.00E−04
−191%


3-methyl-L-histidine
61
0.0012
8.00E−04
83%


Metabolite - 1843
61
0.0012
8.00E−04
524%


cysteine
50
0.0012
8.00E−04
988%


Metabolite - 5187
61
0.0012
8.00E−04
354%


ethylmalonic acid
61
0.0012
8.00E−04
1277%


Metabolite - 2766
61
0.0012
8.00E−04
−2129%


Metabolite - 1104
61
0.0014
8.00E−04
−200%


3-methoxy-L-tyrosine
50
0.0014
9.00E−04
−570%


Metabolite - 3807
61
0.0014
9.00E−04
346%


DL-pipecolic acid
61
0.0015
9.00E−04
296%


Metabolite - 2041
61
0.0015
9.00E−04
198%


malic acid
50
0.0015
9.00E−04
88%


Metabolite - 4331
61
0.0016
9.00E−04
97%


Metabolite - 5166
61
0.0017
0.001
157%


Metabolite - 2111
61
0.0018
0.001
134%


Metabolite - 5167
61
0.0018
0.001
146%


Metabolite - 2867
61
0.0018
0.001
−6300%


3-phospho-d-glycerate
61
0.0018
0.001
−210%


Metabolite - 2109
61
0.0019
0.001
179%


Metabolite - 5232
50
0.0019
0.0011
422%


D-ribose
50
0.002
0.0011
−466%


Metabolite - 3771
61
0.002
0.0011
−163%


alanine
50
0.002
0.0011
86%


Metabolite - 2753
61
0.002
0.0011
227%


xanthosine
50
0.002
0.0011
−391%


arabinose
50
0.002
0.0011
−437%


Metabolite - 1323-possible-4-
61
0.0021
0.0011
311%


sulfobenzyl-alcohol


Metabolite - 3489
61
0.0021
0.0011
−552%


trans-4-hydroxyproline
50
0.0022
0.0011
208%


Metabolite - 3966
61
0.0022
0.0012
159%


Metabolite - 1713
61
0.0025
0.0013
212%


Metabolite - 2237
61
0.0026
0.0013
307%


Metabolite - 2548
61
0.0026
0.0013
97%


Metabolite - 3364
61
0.0026
0.0013
272%


melatonin
50
0.0026
0.0013
227%


Isobar-5-includes-asparagine-ornithine
61
0.0028
0.0014
105%


Metabolite - 1819
61
0.0029
0.0014
69%


inositol
50
0.0029
0.0014
−541%


spermine
50
0.0029
0.0014
−5110%


Metabolite - 1288
61
0.003
0.0014
221%


Metabolite - 5109
61
0.0031
0.0015
385%


thymine
50
0.0031
0.0015
561%


Isobar-19-includes-D-saccharic acid-2-
61
0.0031
0.0015
−213%


deoxy-D-galactose-2-deoxy-D-glucose-


L-fucose-L-rhamnose


Metabolite - 2141
61
0.0032
0.0015
263%


Metabolite - 1327-possible-bilirubin
61
0.0033
0.0015
84%


Metabolite - 2900-
61
0.0034
0.0016
152%


alpha-4-dihydroxybenzenepropanoic
50
0.0034
0.0016
2300%


acid


Metabolite - 3183-possible-gamma-L-
61
0.0035
0.0016
241%


glutamyl-L-phenylalanine-or-aspartame


glutamic acid
50
0.0036
0.0017
114%


5-s-methyl-5-thioadenosine
61
0.0036
0.0017
235%


2-deoxy-D-ribose
61
0.0037
0.0017
68%


4-hydroxy-2-quinolinecarboxylic acid
61
0.0037
0.0017
81%


Metabolite - 4869
61
0.0038
0.0017
184%


Metabolite - 4015
50
0.0038
0.0017
247%


N-acetylserotonin
50
0.0038
0.0017
1007%


allantoin
61
0.0039
0.0018
164%


Metabolite - 2118
61
0.0041
0.0018
−138%


Metabolite - 2323
61
0.0041
0.0018
111%


Isobar-22-includes-glutamic acid-O-
61
0.0041
0.0018
52%


acetyl-L-serine


mercaptopyruvate
61
0.0043
0.0019
130%


3-methylglutaric acid
61
0.0044
0.0019
319%


Metabolite - 2139
61
0.0045
0.0019
165%


Spermidine
50
0.0045
0.0019
−2575%


Metabolite - 3974
61
0.0045
0.0019
114%


azelaic acid
61
0.0045
0.0019
90%


Metabolite - 5186
61
0.0048
0.002
6750%


4-acetamidobutyric acid
61
0.0048
0.002
754%


Metabolite - 5215
50
0.0049
0.002
−151%


dethiobiotin
50
0.0049
0.002
45%


Metabolite - 1496
61
0.0049
0.002
46%


Metabolite - 3955
61
0.0049
0.002
−138%


2-keto-L-gulonic acid
50
0.0054
0.0022
−167%


Metabolite - 5170
61
0.0055
0.0022
−600%


Metabolite - 2466
61
0.006
0.0024
−194%


caffeine
61
0.0064
0.0026
−287%


Isobar-40-includes-Maltotetraose-
61
0.0066
0.0027
−264%


stachyose


Metabolite - 1211
61
0.0069
0.0027
−188%


Metabolite - 4706
61
0.0069
0.0027
304%


Metabolite - 4027
50
0.0069
0.0027
520%


Metabolite - 4150
50
0.007
0.0028
−483%


4-methyl-2-oxopentanoate
61
0.0072
0.0028
194%


Metabolite - 1216
61
0.0073
0.0028
109%


Metabolite - 3837
61
0.0074
0.0029
210%


S-adenosyl-l-homocysteine
61
0.0075
0.0029
72%


Metabolite - 2768
61
0.0077
0.0029
−800%


suberic acid
61
0.008
0.0031
106%


Metabolite - 3554
61
0.0081
0.0031
272%


pyrophosphate
50
0.0081
0.0031
120%


Metabolite - 3996
50
0.0081
0.0031
86%


3-hydroxy-3-methylglutarate
50
0.0084
0.0031
123%


Metabolite - 4615
61
0.0084
0.0031
120%


4-Guanidinobutanoic acid
61
0.0084
0.0031
110%


Metabolite - 2348
61
0.0088
0.0032
151%


Metabolite - 1980
61
0.0088
0.0032
138%


N-5-aminocarbonyl-L-ornithine
50
0.0089
0.0033
177%


Metabolite - 3997
61
0.009
0.0033
1100%


fructose
50
0.0093
0.0034
−336%


Metabolite - 1286
61
0.0093
0.0034
−127%


Metabolite - 1342-possible-
61
0.0094
0.0034
229%


phenylacetylglutamine


Metabolite - 4866
61
0.0099
0.0036
−479%


Metabolite - 3020
50
0.0103
0.0037
97%


Metabolite - 2607
61
0.0103
0.0037
147%


Metabolite - 1609
61
0.0104
0.0037
−227%


Metabolite - 4516
50
0.0115
0.0041
−213%


1-methyladenine
50
0.0116
0.0041
−580%


Metabolite - 2232
61
0.0116
0.0041
−242%


picolinic acid
61
0.0118
0.0041
137%


Metabolite - 2774
61
0.0126
0.0044
96%


Metabolite - 2690
61
0.0127
0.0044
2080%


Metabolite - 3221
61
0.0128
0.0044
107%


Isobar-30-includes-maltotetraose-
61
0.0132
0.0045
−202%


stachyose


Metabolite - 3180
61
0.0134
0.0046
174%


Metabolite - 3220
61
0.0134
0.0046
267%


Metabolite - 3752
61
0.0135
0.0046
1122%


Metabolite - 4787
61
0.0135
0.0046
−540%


Metabolite - 4365
50
0.0146
0.0049
−229%


Metabolite - 3957
61
0.0147
0.0049
59%


DL-cystathionine
50
0.0148
0.0049
271%


2-deoxyuridine
61
0.0149
0.0049
128%


Metabolite - 3379
61
0.0151
0.005
−138%


sarcosine
50
0.0153
0.005
2138%


Metabolite - 4018
61
0.0155
0.0051
813%


cholesterol
50
0.0162
0.0053
33%


5-6-dihydrouracil
61
0.017
0.0055
154%


5-oxoproline
50
0.0174
0.0057
55%


3-amino-isobutyrate
50
0.0177
0.0057
1561%


Metabolite - 1961-retired-glycocholic
61
0.0179
0.0058
691%


acid


Metabolite - 4043
50
0.0185
0.0059
38%


Metabolite - 2981
50
0.0186
0.0059
27%


Metabolite - 3984
61
0.0186
0.0059
800%


tyramine
50
0.0186
0.0059
38%


Metabolite - 3526
61
0.0194
0.0061
127%


Metabolite - 4168
61
0.0198
0.0062
54%


Putrescine
50
0.0199
0.0062
−2967%


Metabolite - 2099
61
0.0204
0.0064
−247%


pyridoxamine-phosphate
61
0.0205
0.0064
−197%


sn-Glycerol-3-phosphate
50
0.0214
0.0066
738%


GABA
50
0.022
0.0068
−192%


Metabolite - 4362
50
0.0223
0.0069
−215%


uridine-5-diphosphoglucose
50
0.0226
0.0069
−142%


saccharopine
61
0.0231
0.007
81%


Metabolite - 3132
61
0.0231
0.007
−195%


Metabolite - 4550
61
0.0234
0.0071
92%


asparagine
50
0.0235
0.0071
81%


Metabolite - 2143
61
0.0238
0.0071
345%


Metabolite - 1970
61
0.0253
0.0076
141%


L-kynurenine
50
0.0258
0.0077
335%


Metabolite - 1129
61
0.0259
0.0077
−183%


Metabolite - 1333
61
0.0263
0.0078
−268%


Metabolite - 2406
61
0.0264
0.0078
238%


Metabolite - 4632
50
0.0266
0.0078
53%


Metabolite - 3123
61
0.0267
0.0078
87%


Metabolite - 1911
61
0.0274
0.008
100%


Metabolite - 2806
61
0.0277
0.0081
−154%


Metabolite - 4014
50
0.0292
0.0085
69%


Metabolite - 1608
61
0.0295
0.0085
−605%


Metabolite - 1974
61
0.0295
0.0085
218%


Metabolite - 3708
61
0.0297
0.0085
46%


Metabolite - 3896
61
0.0297
0.0085
360%


Metabolite - 1303
61
0.0303
0.0086
−256%


Metabolite - 2212
61
0.0308
0.0087
453%


glutarate
61
0.0309
0.0087
155%


Metabolite - 3436
61
0.0316
0.0089
148%


D-sorbitol-6-phosphate
50
0.0319
0.009
−190%


Metabolite - 3430
61
0.0324
0.0091
110%


Metabolite - 3992-
61
0.033
0.0092
−132%


Isobar-1-includes-mannose-fructose-
61
0.034
0.0094
−187%


glucose-galactose-alpha-L-


sorbopyranose-Inositol-D-allose


Metabolite - 2390
61
0.0345
0.0096
343%


Metabolite - 3002
50
0.0346
0.0096
33%


Metabolite - 3545
61
0.0354
0.0097
165%


Metabolite - 1186
61
0.0373
0.0102
−1210%


Metabolite - 1111-possible-
61
0.0375
0.0103
50%


methylnitronitrosoguanidine-or-ethyl-


thiocarbamoylacetate


Metabolite - 5207
50
0.0377
0.0103
−136%


Metabolite - 3016
50
0.0379
0.0103
−184%


Metabolite - 1963
61
0.0393
0.0106
−151%


xylitol
50
0.0393
0.0106
123%


Metabolite - 3022
50
0.0396
0.0107
92%


Metabolite - 2897
61
0.0416
0.0112
92%


uridine-5-monophosphate
61
0.0433
0.0116
−161%


Metabolite - 2027
61
0.044
0.0117
490%


2-deoxyuridine-5-triphosphate
61
0.0444
0.0118
−174%


Metabolite - 3034
50
0.0448
0.0119
67%


3-hydroxybutanoic acid
50
0.0476
0.0125
218%


3-methyl-2-oxovaleric acid
61
0.0477
0.0125
241%


Metabolite - 3980
61
0.0484
0.0127
−169%


niacinamide
61
0.052
0.0135
−138%


Isobar-27-includes-L-kynurenine-alpha-
61
0.052
0.0135
645%


2-diamino-gamma-oxobenzenebutanoic


acid


Metabolite - 4133
50
0.0522
0.0135
120%


Metabolite - 2827
61
0.0526
0.0136
−202%


Metabolite - 5189
61
0.0536
0.0138
110%


Metabolite - 2778
61
0.0537
0.0138
269%


Metabolite - 3027
50
0.0537
0.0138
130%


biliverdin
61
0.0539
0.0138
−151%


Metabolite - 3813
61
0.0547
0.0139
146%


uridine-5-diphosphoglucuronic acid
50
0.055
0.014
129%


Metabolite - 3951
61
0.0551
0.014
64%


phytonadione
50
0.0554
0.014
29%


Metabolite - 3139
61
0.0565
0.0142
71%


Metabolite - 3176-possible-creatine
61
0.0567
0.0142
−129%


Metabolite - 1718
61
0.0568
0.0142
−169%


Metabolite - 3783
61
0.0574
0.0143
−174%


Metabolite - 4616
61
0.0585
0.0145
210%


sorbitol
50
0.0592
0.0147
841%


Metabolite - 2064
61
0.0623
0.0154
54%


cytidine
61
0.0628
0.0155
181%


Metabolite - 5126
61
0.0633
0.0156
−145%


beta-alanine
50
0.0642
0.0157
52%


Metabolite - 4567
61
0.066
0.0161
632%


glucarate
50
0.0686
0.0166
−326%


Metabolite - 3539
61
0.0687
0.0166
143%


Metabolite - 3056
61
0.0688
0.0166
1354%


Metabolite - 2072
61
0.0689
0.0166
368%


Metabolite - 4032
50
0.0745
0.0179
162%


Metabolite - 5229
50
0.0758
0.0182
−144%


beta-nicotinamide-adenine-dinucleotide
61
0.0761
0.0182
2363%


Metabolite - 3960
61
0.0763
0.0182
−140%


Metabolite - 2121
61
0.0771
0.0183
98%


Metabolite - 3238
61
0.0778
0.0185
247%


Metabolite - 3129
61
0.0848
0.02
−118%


25-hydroxycholesterol
50
0.0913
0.0215
11%


Metabolite - 5226
50
0.0977
0.023
100%


Metabolite - 1575
61
0.1
0.0234
−188%


3-nitro-L-tyrosine
50
0.1027
0.024
96%


Metabolite - 1142-possible-5-
61
0.104
0.0242
428%


hydroxypentanoate-or-beta-


hydroxyisovaleric acid


Metabolite - 2250
61
0.1053
0.0245
−150%


gamma-glu-cys
61
0.1128
0.0261
−229%


Metabolite - 2853
61
0.1138
0.0263
79%


Metabolite - 3756
61
0.1144
0.0264
593%


Metabolite - 2368
61
0.115
0.0264
−507%


o-phosphoethanolamine
50
0.1171
0.0268
70%


Metabolite - 1497
61
0.1186
0.0271
−135%


Metabolite - 3475
61
0.1222
0.0278
−148%


Metabolite - 2185
61
0.1229
0.0279
61%


alpha-L-sorbopyranose
50
0.1302
0.0295
−139%


Metabolite - 4512
50
0.1307
0.0295
−167%


histamine
61
0.1324
0.0298
−130%


Metabolite - 1085-possible-isolobinine-
61
0.135
0.0303
34%


or-4-aminoestra-1-3-5-10-triene-3-


17beta-diol


Isobar-18-includes-D-fructose-1-
61
0.1383
0.0309
52%


phosphate-beta-D-fructose-6-


phosphate


Metabolite - 2824
61
0.1384
0.0309
125%


Metabolite - 3848
61
0.1384
0.0309
55%


biotin
61
0.1397
0.0311
−169%


L-homoserine-lactone
61
0.1404
0.0311
−118%


cytidine-5-monophosphate
61
0.1411
0.0312
41%


Metabolite - 3952
61
0.1461
0.0322
−144%


Metabolite - 3576
61
0.1462
0.0322
26%


Metabolite - 2821
61
0.1476
0.0324
291%


Metabolite - 2255
61
0.1483
0.0324
−169%


mannose
50
0.1503
0.0328
−147%


alpha-amino-adipate
50
0.1518
0.033
113%


Metabolite - 3696-retired-isobar-
61
0.152
0.033
230%


glycocheBenignoxycholic acid-


glycodeoxycholic acid


glucose-6-phosphate
50
0.153
0.0331
−144%


Metabolite - 2724
61
0.1543
0.0333
51%


Metabolite - 1616
61
0.1552
0.0334
−158%


Metabolite - 2347
61
0.1567
0.0337
42%


Metabolite - 2313
61
0.1604
0.0344
22%


Metabolite - 2389
61
0.1657
0.0354
22%


mannose-6-phosphate
50
0.1678
0.0357
−200%


Metabolite - 4503
50
0.1692
0.036
426%


serine
50
0.1707
0.0362
22%


Metabolite - 2005
61
0.172
0.0364
52%


Metabolite - 4806
50
0.1728
0.0364
22%


Metabolite - 4030-possible-
61
0.1763
0.0371
52%


glutethimide-or-securinine


Metabolite - 3832-possible-phenol-
61
0.1775
0.0372
199%


sulfate


glucono-gamma-lactone
50
0.1776
0.0372
−143%


Metabolite - 1070
61
0.1836
0.0383
23%


Metabolite - 4019
50
0.1844
0.0384
32%


Metabolite - 4355
50
0.1854
0.0385
22%


N-acetyl-D-glucosamine
50
0.186
0.0385
31%


Metabolite - 2198
61
0.1861
0.0385
−144%


Metabolite - 4053
50
0.1928
0.0397
45%


Isobar-3-includes-inositol-1-phosphate-
61
0.1941
0.0399
−127%


mannose-6-phosphate-glucose-6-


phosphate-D-mannose-1-phosphate-


alpha-D-glucose-1-phosphate-alpha-D-


galactose-1-phosphate


maltose
50
0.1978
0.0406
426%


Metabolite - 4868-possible-Bradykinin
61
0.1998
0.0409
−120%


Metabolite - 4497
50
0.2013
0.0411
−132%


Isobar-4-includes-Gluconic acid-DL-
61
0.2053
0.0418
−129%


arabinose-D-ribose-L-xylose-DL-lyxose-


D-xylulose


Metabolite - 1457
61
0.2062
0.0419
41%


Metabolite - 2691
61
0.2102
0.0426
48%


Metabolite - 2075
61
0.2122
0.0428
−161%


dulcitol
50
0.2122
0.0428
−146%


Metabolite - 4931
61
0.2153
0.0433
30%


orotidine-5-phosphate
61
0.2187
0.0439
81%


Metabolite - 3074
50
0.2196
0.0439
86%


hypotaurine
50
0.221
0.044
60%


N-acetyl-D-galactosamine
50
0.2211
0.044
33%


Metabolite - 4116
61
0.2274
0.0452
16%


Metabolite - 3476
61
0.2356
0.0467
−137%


adenine
50
0.2383
0.0471
58%


N-6-trimethyl-l-lysine
61
0.2389
0.0471
−132%


2-deoxy-D-glucose
50
0.2399
0.0472
−142%


Metabolite - 3317
61
0.2414
0.0474
42%


glutamine
50
0.2426
0.0475
55%


Metabolite - 1573
61
0.247
0.0482
42%


Isobar-32-includes-N-acetyl-D-
61
0.2551
0.0497
24%


glucosamine-N-acetyl-D-mannosamine


Metabolite - 1248-possible-avermectin-
61
0.2596
0.0505
−135%


aglycone


Metabolite - 2388
61
0.2679
0.052
19%


Metabolite - 2546
61
0.2715
0.0525
91%


Metabolite - 1113-possible-
61
0.28
0.054
23%


acetylcarnitine-or-isopentyl-adenine


alpha-D-ribose-5-phosphate
50
0.2826
0.0544
−129%


Metabolite - 5227
50
0.2888
0.0555
1117%


Metabolite - 3534
61
0.2998
0.0575
58%


2-acetamido-1-amino-1-2-dideoxy-beta-
50
0.3037
0.0581
25%


D-glucopyranose


Metabolite - 5211
50
0.3045
0.0581
−184%


Metabolite - 1653
61
0.3126
0.0595
−127%


Metabolite - 2036
61
0.3211
0.061
115%


Metabolite - 4003
61
0.3245
0.0615
−124%


Metabolite - 4058
50
0.3276
0.0619
27%


Metabolite - 2055
61
0.3345
0.0631
−122%


3-phospho-l-serine
61
0.3436
0.0646
−109%


Metabolite - 3073
50
0.3654
0.0686
45%


Metabolite - 4272
50
0.3717
0.0696
−119%


Metabolite - 1203-possible-
61
0.3764
0.0703
−140%


acetylbrowniine-tricornine-germine-or-


veracevine


Metabolite - 4448
61
0.4001
0.0746
−116%


Metabolite - 2846
61
0.4122
0.0767
80%


Metabolite - 5213
50
0.4147
0.077
−118%


galactose
50
0.4216
0.0781
17%


hippuric acid
61
0.4252
0.0786
−139%


Metabolite - 3514-retired-topiramate
61
0.4327
0.0798
−341%


Isobar-21-includes-gamma-
61
0.4395
0.0808
37%


aminobutyryl-L-histidine-L-anserine


uridine
61
0.4426
0.0812
−108%


Metabolite - 1330
61
0.4441
0.0813
57%


Metabolite - 3994
61
0.4454
0.0814
−128%


Metabolite - 4017
50
0.4508
0.0822
16%


Metabolite - 5147
61
0.461
0.0838
196%


Metabolite - 4637
50
0.4761
0.0864
12%


Metabolite - 3668
61
0.477
0.0864
23%


Metabolite - 3365
61
0.4807
0.0868
−127%


Metabolite - 1455
61
0.4815
0.0868
−171%


Metabolite - 4096-gamma-glu-gly-leu-
61
0.4858
0.0874
−109%


Metabolite - 1187
61
0.4937
0.0886
−126%


Metabolite - 2194
61
0.5147
0.0922
30%


Metabolite - 3543
61
0.5175
0.0925
44%


possible-ISOBAR-DL-aspartic acid-
50
0.519
0.0925
22%


Metabolite - 3522
61
0.5205
0.0925
−231%


Metabolite - 2105
61
0.521
0.0925
15%


dihydroxyacetone-phosphate
61
0.532
0.0942
−116%


Metabolite - 3051
61
0.5346
0.0945
29%


Metabolite - 3755
61
0.5481
0.0967
12%


Metabolite - 3604
61
0.5512
0.097
−129%


Metabolite - 4238
61
0.5582
0.098
23%


Metabolite - 4523
50
0.5592
0.098
13%


Metabolite - 2407
61
0.5602
0.098
−133%


Metabolite - 4354
50
0.5857
0.1021
−112%


Metabolite - 2129
61
0.5869
0.1021
17%


Metabolite - 4002
50
0.5873
0.1021
13%


Metabolite - 1392
61
0.5947
0.1031
36%


6-phosphogluconic acid
61
0.5976
0.1034
8%


phosphoenolpyruvate
50
0.6017
0.1039
16%


Carnosine
61
0.6048
0.1042
−112%


alpha-keto-glutarate
61
0.6073
0.1044
47%


Metabolite - 3484
61
0.6115
0.1049
27%


Metabolite - 2279
61
0.6193
0.1061
−115%


Metabolite - 2074
61
0.6245
0.1067
−118%


Isobar-31-includes-maltotriose-
61
0.6315
0.1077
−115%


melezitose


N-acetylneuraminate
61
0.639
0.1088
11%


ascorbic acid
50
0.6412
0.1089
18%


Metabolite - 4084
50
0.6527
0.1106
−104%


Metabolite - 1088
61
0.6537
0.1106
16%


Metabolite - 4020
50
0.6567
0.1108
12%


creatinine
61
0.6624
0.1116
6%


Metabolite - 2174
61
0.6687
0.1124
15%


Metabolite - 3498
61
0.6739
0.1129
12%


Metabolite - 3401
61
0.6742
0.1129
16%


succinate
50
0.6845
0.1144
−120%


L-histidinol
61
0.6889
0.1149
−108%


Metabolite - 4667
61
0.6922
0.1152
−109%


Metabolite - 4510
50
0.6961
0.1156
9%


Metabolite - 3099
50
0.6979
0.1157
7%


Metabolite - 2056
61
0.7004
0.1158
−106%


Metabolite - 1183
61
0.7152
0.118
−118%


beta-D-lactose
50
0.7236
0.1192
14%


Metabolite - 4796
50
0.7305
0.1201
14%


Metabolite - 4235
61
0.7549
0.1238
−126%


Metabolite - 4514
50
0.7707
0.1262
−105%


Metabolite - 3531
61
0.7817
0.1277
−126%


Metabolite - 5089
61
0.783
0.1277
−121%


benzoic acid
50
0.797
0.1297
−103%


Isobar-17-includes-arginine-N-alpha-
61
0.808
0.1312
6%


acetyl-ornithine


ornithine
50
0.8172
0.1325
−106%


Metabolite - 2319
61
0.8211
0.1328
−111%


cystine
50
0.8239
0.1329
−104%


Metabolite - 5086
61
0.8247
0.1329
−110%


Metabolite - 3189
61
0.8275
0.1331
7%


guanine
50
0.8461
0.1356
8%


Metabolite - 3517
61
0.8465
0.1356
9%


Metabolite - 3040
50
0.8495
0.1358
−104%


Metabolite - 2558
61
0.8782
0.1401
7%


Metabolite - 2180
61
0.8839
0.1408
−104%


arginino-succinate
61
0.8933
0.1419
−103%


Metabolite - 4080
50
0.8946
0.1419
4%


Metabolite - 2688
61
0.9212
0.1459
−101%


aspartate
61
0.9268
0.1463
2%


Metabolite - 2703
61
0.9278
0.1463
−103%


Metabolite - 5087
61
0.9434
0.1485
−104%


Metabolite - 3694
61
0.9614
0.1509
−102%


Metabolite - 1979-Cl-adduct-of-
61
0.9624
0.1509
−101%


C6H10O5


Metabolite - 1975
61
0.9674
0.1514
1%


Metabolite - 4271
50
0.9952
0.1555
1%
















TABLE 3







Prostate Cancer Biomarkers from subjects with Metastatic, High


Grade Prostate Cancer compared to subjects with Lower Grade Prostate


Cancer.















%






Change






in high






grade


COMPOUND
Library
p-value
q-value
PCA














inosine
61
<0.0001
<0.0001
−63%


Metabolite - 3390
61
<0.0001
<0.0001
−69%


octadecanoic acid
50
<0.0001
<0.0001
89%


Metabolite - 2-Aminoethyl-phosphonate
61
<0.0001
<0.0001
−78%


glycerol
50
<0.0001
<0.0001
200%


n-hexadecanoic acid
50
<0.0001
<0.0001
241%


leucine
50
<0.0001
1.00E−04
96%


Metabolite - 1498
61
<0.0001
2.00E−04
95%


Metabolite - 4013
61
<0.0001
2.00E−04
418%


Isobar-24-includes-L-arabitol-adonitol
61
<0.0001
2.00E−04
183%


4-hydroxyphenylpyruvate
61
<0.0001
2.00E−04
−71%


Putrescine
50
<0.0001
2.00E−04
−81%


glycerate
61
<0.0001
2.00E−04
235%


xanthine
61
<0.0001
2.00E−04
331%


uridine
61
<0.0001
2.00E−04
−46%


Metabolite - 1597
61
<0.0001
3.00E−04
63%


Metabolite - 4611
50
<0.0001
3.00E−04
388%


uracil
50
1.00E−04
5.00E−04
351%


3-phospho-d-glycerate
61
1.00E−04
6.00E−04
−53%


tetradecanoic acid
50
1.00E−04
6.00E−04
472%


Metabolite - 3102
50
1.00E−04
6.00E−04
716%


inositol
50
1.00E−04
6.00E−04
−74%


riboflavine
61
1.00E−04
6.00E−04
77%


Metabolite - 3772
61
1.00E−04
6.00E−04
76%


Metabolite - 3085
50
1.00E−04
6.00E−04
−53%


9-12-octadecadienoic acid-z-z-
50
1.00E−04
6.00E−04
256%


anthranilic acid
50
1.00E−04
6.00E−04
57%


n-dodecanoate
50
1.00E−04
6.00E−04
351%


Metabolite - 3215
61
1.00E−04
6.00E−04
157%


palmitoleic acid
50
1.00E−04
6.00E−04
825%


urea
50
1.00E−04
6.00E−04
241%


Metabolite - 4620
61
1.00E−04
6.00E−04
854%


valine
50
2.00E−04
7.00E−04
47%


Metabolite - 2466
61
2.00E−04
7.00E−04
−74%


Metabolite - 1349
61
2.00E−04
7.00E−04
−88%


Metabolite - 4075
50
2.00E−04
8.00E−04
689%


Metabolite - 3808
61
2.00E−04
8.00E−04
−72%


Metabolite - 5209
50
2.00E−04
8.00E−04
−78%


Metabolite - 4134
50
2.00E−04
8.00E−04
444%


Metabolite - 1116
61
2.00E−04
8.00E−04
476%


Metabolite - 4150
50
2.00E−04
8.00E−04
−68%


Metabolite - 3014
50
3.00E−04
9.00E−04
322%


Metabolite - 2548
61
3.00E−04
9.00E−04
189%


Metabolite - 3178
61
3.00E−04
0.001
−88%


uric acid
61
3.00E−04
0.001
200%


Metabolite - 1351
61
3.00E−04
0.001
291%


Metabolite - 4046
50
3.00E−04
0.001
688%


Metabolite - 1329
61
4.00E−04
0.001
147%


Metabolite - 4649
61
4.00E−04
0.0011
224%


Metabolite - 3992-
61
4.00E−04
0.0011
−33%


Metabolite - 2272
61
4.00E−04
0.0012
176%


Metabolite - 2181
61
5.00E−04
0.0013
135%


Metabolite - 4869
61
5.00E−04
0.0013
361%


arabinose
50
5.00E−04
0.0013
−73%


D-ribose
50
5.00E−04
0.0013
−74%


xanthosine
50
5.00E−04
0.0013
−69%


Isobar-19-includes-D-saccharic acid-2-
61
6.00E−04
0.0015
−53%


deoxy-D-galactose-2-deoxy-D-glucose-L-


fucose-L-rhamnose


3-methoxy-L-tyrosine
50
6.00E−04
0.0015
−75%


2-keto-L-gulonic acid
50
6.00E−04
0.0015
−47%


Metabolite - 2766
61
7.00E−04
0.0015
−93%


lactate
50
7.00E−04
0.0017
38%


Metabolite - 3893
61
7.00E−04
0.0017
−85%


tryptophan
61
8.00E−04
0.0017
53%


phenylalanine
61
8.00E−04
0.0017
43%


Metabolite - 1819
61
8.00E−04
0.0018
99%


Metabolite - 1323-possible-4-sulfobenzyl-
61
9.00E−04
0.0019
495%


alcohol


Metabolite - 3123
61
0.001
0.0021
223%


guanosine
61
0.001
0.0022
−48%


proline
50
0.0011
0.0022
94%


N-acetyl-D-galactosamine
50
0.0011
0.0022
−58%


Metabolite - 2255
61
0.0011
0.0022
−59%


pantothenic acid
61
0.0011
0.0022
89%


Metabolite - 5212
50
0.0011
0.0022
−80%


DL-pipecolic acid
61
0.0012
0.0023
329%


Metabolite - 5187
61
0.0012
0.0023
348%


Metabolite - 5207
50
0.0012
0.0023
−35%


creatinine
61
0.0013
0.0023
41%


Metabolite - 4518
50
0.0013
0.0024
490%


Metabolite - 3807
61
0.0013
0.0024
363%


Metabolite - 2924
50
0.0014
0.0024
187%


Metabolite - 4617
61
0.0014
0.0024
107%


Metabolite - 3165
61
0.0014
0.0024
39%


Metabolite - 4428
61
0.0014
0.0024
155%


Metabolite - 5107
61
0.0014
0.0024
170%


Metabolite - 3833
61
0.0015
0.0024
188%


Metabolite - 2607
61
0.0015
0.0024
348%


ethylmalonic acid
61
0.0015
0.0024
894%


Metabolite - 3837
61
0.0017
0.0028
363%


Metabolite - 3132
61
0.0017
0.0028
−58%


Metabolite - 4051
50
0.0018
0.0028
266%


Isobar-3-includes-inositol-1-phosphate-
61
0.0018
0.0029
−52%


mannose-6-phosphate-glucose-6-


phosphate-D-mannose-1-phosphate-alpha-


D-glucose-1-phosphate-alpha-D-galactose-


1-phosphate


Metabolite - 3003
50
0.0019
0.0029
94%


allantoin
61
0.002
0.0031
211%


Metabolite - 3138
61
0.0021
0.0032
128%


catechol
61
0.0021
0.0032
292%


heptadecanoic acid
50
0.0022
0.0032
71%


Metabolite - 1843
61
0.0022
0.0033
361%


N-6-trimethyl-l-lysine
61
0.0023
0.0033
−44%


phosphate
50
0.0024
0.0034
49%


Isobar-2-includes-3-amino-isobutyrate-2-
61
0.0025
0.0035
121%


amino-butyrate-4-aminobutanoic acid-


dimethylglycine-choline-


niacinamide
61
0.0025
0.0036
−35%


Metabolite - 2237
61
0.0026
0.0037
291%


Metabolite - 2567
61
0.0028
0.0038
101%


S-5-adenosyl-L-methionine
61
0.0028
0.0038
153%


Metabolite - 3489
61
0.0028
0.0038
−81%


Metabolite - 2867
61
0.0029
0.0039
−99%


1-methyladenosine
61
0.0029
0.0039
260%


thymine
50
0.0031
0.0041
561%


Metabolite - 3543
61
0.0032
0.0041
174%


D-sorbitol-6-phosphate
50
0.0032
0.0041
−66%


Metabolite - 2250
61
0.0033
0.0042
−61%


citric acid
50
0.0034
0.0043
−92%


L-alpha-glycerophosphorylcholine
61
0.0035
0.0043
192%


Metabolite - 1288
61
0.0035
0.0043
212%


elaidic acid
50
0.0035
0.0044
241%


alpha-4-dihydroxybenzenepropanoic acid
50
0.0036
0.0044
1900%


Metabolite - 3996
50
0.0036
0.0044
104%


Metabolite - 2711
61
0.0037
0.0044
65%


mannose-6-phosphate
50
0.0038
0.0045
−82%


Metabolite - 1457
61
0.0038
0.0045
115%


Metabolite - 3364
61
0.0039
0.0046
232%


glyceric acid
50
0.0039
0.0046
78%


Metabolite - 4615
61
0.004
0.0046
154%


uridine-5-diphosphoglucose
50
0.004
0.0046
−35%


Metabolite - 2323
61
0.0041
0.0047
111%


Metabolite - 1333
61
0.0042
0.0047
−71%


Metabolite - 3966
61
0.0042
0.0047
171%


3-methylglutaric acid
61
0.0043
0.0047
319%


mercaptopyruvate
61
0.0043
0.0047
130%


D-allose
50
0.0043
0.0047
−87%


Metabolite - 1342-possible-
61
0.0043
0.0047
286%


phenylacetylglutamine


isoleucine
50
0.0044
0.0047
33%


Metabolite - 3044
61
0.0046
0.0049
120%


4-acetamidobutyric acid
61
0.0048
0.0051
754%


3-phospho-l-serine
61
0.0051
0.0053
−22%


Metabolite - 3531
61
0.0051
0.0053
160%


Metabolite - 3514-retired-topiramate
61
0.0053
0.0055
170%


inositol-1-phosphate
50
0.0054
0.0055
88%


Metabolite - 1392
61
0.0057
0.0059
164%


Metabolite - 2973
50
0.006
0.006
−38%


Metabolite - 5214
50
0.0062
0.0062
−71%


Metabolite - 1394-possible-Losartan
61
0.0063
0.0063
109%


Metabolite - 4550
61
0.0065
0.0064
95%


Metabolite - 3816
61
0.0065
0.0064
−92%


Metabolite - 2141
61
0.0068
0.0066
181%


Metabolite - 3526
61
0.0075
0.0072
196%


Metabolite - 1831-possible-Cl-adduct-of-
61
0.0078
0.0075
86%


citrulline


Metabolite - 1330
61
0.0079
0.0076
216%


spermine
50
0.0085
0.0081
−91%


Metabolite - 5186
61
0.0087
0.0081
879%


Metabolite - 4637
50
0.0087
0.0081
−28%


Metabolite - 3708
61
0.0087
0.0081
61%


Metabolite - 1496
61
0.0087
0.0081
46%


3-methyl-L-histidine
61
0.009
0.0082
51%


Metabolite - 3668
61
0.009
0.0082
132%


taurine
61
0.0091
0.0083
−42%


Metabolite - 5210
50
0.0092
0.0083
−44%


histidine
50
0.0093
0.0083
39%


Metabolite - 3522
61
0.0094
0.0084
182%


Metabolite - 4014
50
0.01
0.0088
104%


quinolinic acid
61
0.0101
0.0088
93%


Metabolite - 1465
61
0.0101
0.0088
124%


Metabolite - 3539
61
0.0102
0.0089
460%


Metabolite - 1186
61
0.0105
0.0091
−82%


arachidonic acid
50
0.0106
0.0091
74%


Metabolite - 3998
50
0.0108
0.0092
32%


carnitine
61
0.0111
0.0094
74%


Metabolite - 2900-
61
0.0111
0.0094
103%


alanine
50
0.0115
0.0096
54%


Isobar-6-includes-valine-betaine
61
0.0115
0.0096
30%


Metabolite - 3997
61
0.0116
0.0096
740%


Metabolite - 3554
61
0.0121
0.0099
226%


Metabolite - 2111
61
0.0121
0.0099
76%


Metabolite - 4019
50
0.0125
0.0102
−35%


Metabolite - 3221
61
0.0128
0.0103
107%


Metabolite - 5110
61
0.0132
0.0107
131%


N-acetyl-D-glucosamine
50
0.0134
0.0107
−42%


4-Guanidinobutanoic acid
61
0.0136
0.0108
98%


5-s-methyl-5-thioadenosine
61
0.0137
0.0108
152%


Metabolite - 5087
61
0.014
0.011
105%


ribulose-5-phosphate
50
0.014
0.011
−51%


Metabolite - 3020
50
0.0146
0.0114
76%


Metabolite - 3436
61
0.0152
0.0118
213%


3-amino-isobutyrate
50
0.0162
0.0125
2172%


Metabolite - 3955
61
0.0171
0.0131
−25%


Metabolite - 2897
61
0.0171
0.0131
121%


Metabolite - 3220
61
0.0175
0.0133
235%


Metabolite - 5089
61
0.0177
0.0134
133%


Metabolite - 2690
61
0.0191
0.0142
784%


suberic acid
61
0.0191
0.0142
79%


Metabolite - 2688
61
0.0191
0.0142
−18%


Metabolite - 4235
61
0.0193
0.0142
140%


Metabolite - 1974
61
0.0194
0.0142
289%


gamma-L-glutamyl-L-glutamine
61
0.0195
0.0142
−68%


Metabolite - 2347
61
0.02
0.0145
69%


Metabolite - 4706
61
0.0201
0.0145
184%


picolinic acid
61
0.0201
0.0145
131%


Metabolite - 2143
61
0.0204
0.0146
408%


Metabolite - 4866
61
0.0209
0.0149
−79%


Metabolite - 4018
61
0.0212
0.015
564%


2-acetamido-1-amino-1-2-dideoxy-beta-D-
50
0.0214
0.0151
−46%


glucopyranose


adenosine
61
0.022
0.0155
−56%


sarcosine
50
0.0225
0.0157
795%


Metabolite - 1069-possible-
61
0.0229
0.0159
−79%


dehydroepiandrosterone-sulfate-


DL-cystathionine
50
0.0233
0.0161
203%


Metabolite - 5086
61
0.0236
0.0163
53%


Metabolite - 3064
61
0.0242
0.0166
96%


L-kynurenine
50
0.0252
0.0172
347%


pyrophosphate
50
0.0256
0.0173
84%


Spermidine
50
0.0257
0.0173
−92%


Metabolite - 1961-retired-glycocholic acid
61
0.0257
0.0173
444%


Metabolite - 1608
61
0.0261
0.0174
−60%


Metabolite - 5109
61
0.0261
0.0174
156%


3-hydroxybutanoic acid
50
0.0263
0.0174
305%


Metabolite - 1114
61
0.0264
0.0174
33%


Metabolite - 5232
50
0.0267
0.0176
150%


N-acetylserotonin
50
0.0272
0.0178
192%


Metabolite - 3984
61
0.0287
0.0187
468%


Metabolite - 1595-possible-glutathione-
61
0.0293
0.019
−66%


metabolite


trans-4-hydroxyproline
50
0.0308
0.0199
89%


Metabolite - 4593
50
0.0311
0.02
56%


Carnosine
61
0.0326
0.0209
63%


Metabolite - 2139
61
0.0342
0.0218
88%


beta-alanine
50
0.0345
0.0218
74%


Metabolite - 2390
61
0.0345
0.0218
343%


Metabolite - 2292
61
0.035
0.022
−76%


Metabolite - 2075
61
0.0355
0.0222
−75%


Metabolite - 4331
61
0.0357
0.0222
56%


Metabolite - 2108
61
0.0374
0.0232
44%


Metabolite - 3370
61
0.0394
0.0242
31%


Metabolite - 4168
61
0.0394
0.0242
49%


Metabolite - 4868-possible-Bradykinin
61
0.0397
0.0243
−61%


DL-homocysteine
61
0.0409
0.0249
45%


sn-Glycerol-3-phosphate
50
0.0414
0.0251
322%


Metabolite - 3139
61
0.0421
0.0254
−31%


Metabolite - 5126
61
0.0422
0.0254
−38%


Metabolite - 1129
61
0.0427
0.0256
−56%


Metabolite - 1203-possible-acetylbrowniine-
61
0.0434
0.0258
−62%


tricornine-germine-or-veracevine


Metabolite - 5108
61
0.0435
0.0258
95%


Metabolite - 4027
50
0.0437
0.0259
153%


Metabolite - 2099
61
0.0442
0.0261
−68%


arginino-succinate
61
0.0455
0.0267
−50%


L-allo-threonine
50
0.0477
0.0279
26%


Metabolite - 2853
61
0.0497
0.029
124%


Metabolite - 1576
61
0.0509
0.0295
41%


Metabolite - 1303
61
0.0513
0.0296
−60%


noradrenaline
50
0.0515
0.0296
26%


Metabolite - 1713
61
0.0518
0.0297
71%


Metabolite - 2778
61
0.0537
0.0305
269%


sorbitol
50
0.0539
0.0305
1085%


Metabolite - 1718
61
0.0539
0.0305
−51%


Metabolite - 4567
61
0.0542
0.0305
1058%


gamma-glu-cys
61
0.0543
0.0305
−73%


caffeine
61
0.0545
0.0305
−71%


Metabolite - 5167
61
0.0553
0.0308
72%


fumaric acid
50
0.0577
0.032
63%


Metabolite - 3379
61
0.0578
0.032
−26%


Metabolite - 1970
61
0.059
0.0324
102%


Metabolite - 2406
61
0.0591
0.0324
159%


threonine
50
0.0604
0.033
24%


Metabolite - 2072
61
0.0621
0.0338
417%


Metabolite - 5229
50
0.0624
0.0339
−32%


Metabolite - 3960
61
0.0638
0.0343
−30%


Metabolite - 3022
50
0.0639
0.0343
79%


Metabolite - 5166
61
0.064
0.0343
72%


Metabolite - 3056
61
0.0644
0.0344
1785%


Metabolite - 2027
61
0.0656
0.0349
301%


Metabolite - 4015
50
0.0678
0.0359
72%


Metabolite - 2118
61
0.0694
0.0366
−26%


Metabolite - 1070
61
0.0695
0.0366
−41%


Metabolite - 4516
50
0.0724
0.038
−50%


Metabolite - 4365
50
0.0728
0.038
−56%


Metabolite - 2806
61
0.0732
0.038
−26%


Metabolite - 3896
61
0.0733
0.038
179%


glutathione-reduced
61
0.0737
0.0381
−78%


Metabolite - 3180
61
0.0751
0.0387
88%


3-methyl-2-oxovaleric acid
61
0.0755
0.0388
170%


Metabolite - 3073
50
0.0767
0.0392
138%


Metabolite - 1327-possible-bilirubin
61
0.0774
0.0395
41%


Metabolite - 3238
61
0.0778
0.0395
247%


L-homoserine-lactone
61
0.0786
0.0398
−24%


uridine-5-diphosphoglucuronic acid
50
0.0813
0.041
114%


Metabolite - 1248-possible-avermectin-
61
0.0825
0.0414
−39%


aglycone


Metabolite - 3974
61
0.0853
0.0427
55%


Isobar-27-includes-L-kynurenine-alpha-2-
61
0.0883
0.0441
293%


diamino-gamma-oxobenzenebutanoic acid


tyrosine
61
0.0893
0.0444
19%


Metabolite - 2105
61
0.0921
0.0456
−42%


Metabolite - 4017
50
0.0939
0.0462
−24%


saccharopine
61
0.094
0.0462
47%


Metabolite - 3002
50
0.0977
0.0479
25%


Metabolite - 4512
50
0.0991
0.0484
−55%


Metabolite - 1977
61
0.1008
0.0491
51%


Metabolite - 3771
61
0.1044
0.0506
−25%


Metabolite - 3498
61
0.1048
0.0506
−28%


aspartate
61
0.1051
0.0506
−34%


Metabolite - 1142-possible-5-
61
0.1082
0.0519
407%


hydroxypentanoate-or-beta-


hydroxyisovaleric acid


Metabolite - 4058
50
0.1102
0.0528
−38%


Metabolite - 3980
61
0.1154
0.0551
−39%


Metabolite - 1111-possible-
61
0.1163
0.0552
−22%


methylnitronitrosoguanidine-or-ethyl-


thiocarbamoylacetate


5-hydroxyindoleacetate
50
0.1165
0.0552
−90%


Metabolite - 2121
61
0.1176
0.0556
84%


Metabolite - 3183-possible-gamma-L-
61
0.1218
0.0574
64%


glutamyl-L-phenylalanine-or-aspartame


Metabolite - 3951
61
0.1225
0.0575
45%


Metabolite - 3832-possible-phenol-sulfate
61
0.1246
0.0583
327%


Metabolite - 2703
61
0.1261
0.0588
−26%


Metabolite - 3756
61
0.1282
0.0596
454%


Metabolite - 2546
61
0.1302
0.0603
197%


Metabolite - 3016
50
0.1372
0.0633
−39%


Metabolite - 3810
61
0.1419
0.0653
−31%


Metabolite - 3534
61
0.1426
0.0654
67%


melatonin
50
0.1438
0.0657
55%


Metabolite - 2821
61
0.1453
0.0662
300%


Metabolite - 1497
61
0.1469
0.0668
−25%


alpha-L-sorbopyranose
50
0.1505
0.0682
−26%


Metabolite - 3696-retired-isobar-
61
0.152
0.0686
230%


glycochenodeoxycholic acid-


glycodeoxycholic acid


Metabolite - 2724
61
0.1527
0.0687
52%


Metabolite - 4787
61
0.1533
0.0688
−84%


Metabolite - 4117-possible-propranolol-or-2-
61
0.1541
0.0689
39%


heptyl-3-hydroxy-quinolone


Metabolite - 1573
61
0.1548
0.069
56%


beta-nicotinamide-adenine-dinucleotide
61
0.1581
0.0702
352%


alpha-D-ribose-5-phosphate
50
0.1585
0.0702
−29%


Metabolite - 1593
61
0.16
0.0707
−56%


glycine
50
0.1614
0.0711
20%


glutarate
61
0.1633
0.0717
73%


succinate
50
0.1697
0.074
84%


Metabolite - 1113-possible-acetylcarnitine-
61
0.1697
0.074
30%


or-isopentyl-adenine


Metabolite - 3034
50
0.1726
0.0751
38%


Metabolite - 3848
61
0.1771
0.0767
−29%


Metabolite - 5228
50
0.1777
0.0767
22%


Metabolite - 3099
50
0.1779
0.0767
−25%


GABA
50
0.1788
0.0768
−35%


serine
50
0.1792
0.0768
−13%


Metabolite - 4133
50
0.1803
0.077
64%


Metabolite - 2036
61
0.1835
0.078
246%


Metabolite - 2824
61
0.1838
0.078
98%


possible-ISOBAR-DL-aspartic acid-
50
0.1848
0.0782
−29%


maltose
50
0.1852
0.0782
504%


Metabolite - 4503
50
0.1887
0.0794
335%


Metabolite - 2827
61
0.1937
0.0813
−56%


Metabolite - 3129
61
0.1989
0.0832
−13%


Metabolite - 1616
61
0.1999
0.0834
−64%


Metabolite - 3604
61
0.2032
0.0845
−40%


Metabolite - 5128
61
0.2076
0.0861
−72%


Isobar-5-includes-asparagine-ornithine
61
0.2092
0.0865
30%


1-7-dihydro-6h-purin-6-one
61
0.2113
0.0867
14%


1-methyladenine
50
0.2113
0.0867
−83%


Metabolite - 4030-possible-glutethimide-or-
61
0.2115
0.0867
−28%


securinine


ornithine
50
0.2134
0.0872
−20%


Metabolite - 1679
61
0.2163
0.0881
56%


methionine
61
0.218
0.0886
17%


biotin
61
0.2198
0.0891
−35%


Metabolite - 4116
61
0.2206
0.0892
−13%


Metabolite - 1963
61
0.229
0.0923
−27%


Metabolite - 1575
61
0.2338
0.0938
−37%


S-adenosyl-l-homocysteine
61
0.234
0.0938
22%


dethiobiotin
50
0.2429
0.0971
−11%


Metabolite - 1216
61
0.2446
0.0975
36%


Metabolite - 1455
61
0.2458
0.0977
206%


Metabolite - 4080
50
0.2467
0.0977
−39%


biliverdin
61
0.2525
0.0998
−25%


Metabolite - 5226
50
0.2569
0.1012
50%


25-hydroxycholesterol
50
0.258
0.1014
−6%


Metabolite - 2129
61
0.2623
0.1028
−44%


N-acetylneuraminate
61
0.265
0.1036
29%


Metabolite - 2109
61
0.2658
0.1036
27%


Metabolite - 3517
61
0.2721
0.1057
67%


Metabolite - 4667
61
0.2746
0.1064
−22%


cytidine-5-monophosphate
61
0.2754
0.1064
27%


Metabolite - 4003
61
0.276
0.1064
−19%


Metabolite - 3074
50
0.2779
0.1069
80%


Metabolite - 2774
61
0.2815
0.1079
34%


Metabolite - 5170
61
0.2827
0.1081
−98%


Metabolite - 2768
61
0.285
0.1087
−99%


dihydroxyacetone-phosphate
61
0.295
0.1122
−22%


glucarate
50
0.3014
0.1144
−73%


Metabolite - 2055
61
0.303
0.1145
27%


Metabolite - 2368
61
0.3043
0.1145
−87%


pyridoxamine-phosphate
61
0.3047
0.1145
−24%


phosphoenolpyruvate
50
0.3051
0.1145
−43%


fructose
50
0.3065
0.1148
−44%


Metabolite - 5227
50
0.3077
0.1149
740%


Metabolite - 1088
61
0.3104
0.1155
−36%


2-deoxy-D-ribose
61
0.311
0.1155
17%


phytonadione
50
0.3221
0.1194
−11%


Metabolite - 1609
61
0.3244
0.1199
−33%


malic acid
50
0.3288
0.1212
17%


Metabolite - 4796
50
0.3315
0.1218
26%


6-phosphogluconic acid
61
0.3322
0.1218
16%


benzoic acid
50
0.333
0.1218
13%


Metabolite - 1211
61
0.3356
0.1224
10%


Metabolite - 4806
50
0.3385
0.1232
18%


2-deoxyuridine
61
0.3422
0.1237
31%


cholesterol
50
0.3424
0.1237
−9%


Metabolite - 3545
61
0.3426
0.1237
51%


Isobar-1-includes-mannose-fructose-
61
0.3458
0.1246
−17%


glucose-galactose-alpha-L-sorbopyranose-


Inositol-D-allose


Metabolite - 2056
61
0.3473
0.1248
18%


3-hydroxy-3-methylglutarate
50
0.3496
0.1253
22%


4-hydroxy-2-quinolinecarboxylic acid
61
0.3526
0.1261
−14%


Metabolite - 1653
61
0.3592
0.1277
−25%


xylitol
50
0.3596
0.1277
35%


Metabolite - 2348
61
0.3597
0.1277
48%


Metabolite - 3401
61
0.3637
0.1287
41%


Isobar-40-includes-Maltotetraose-stachyose
61
0.3704
0.1308
−36%


hippuric acid
61
0.3719
0.131
−29%


glutamic acid
50
0.3743
0.1315
17%


Metabolite - 2232
61
0.3753
0.1315
−36%


Metabolite - 4362
50
0.381
0.1332
−21%


Isobar-4-includes-Gluconic acid-DL-
61
0.3854
0.1344
−23%


arabinose-D-ribose-L-xylose-DL-lyxose-D-


xylulose


Metabolite - 3430
61
0.3874
0.1348
29%


Metabolite - 2313
61
0.3923
0.1361
14%


5-6-dihydrouracil
61
0.3941
0.1361
31%


Metabolite - 1104
61
0.3943
0.1361
−23%


Metabolite - 4355
50
0.3949
0.1361
−10%


Metabolite - 2074
61
0.4055
0.1394
45%


Metabolite - 2981
50
0.4071
0.1396
8%


Metabolite - 3094
50
0.4099
0.1402
−8%


Metabolite - 5189
61
0.4199
0.1433
−42%


Metabolite - 2194
61
0.4272
0.1454
43%


Metabolite - 2558
61
0.4305
0.146
35%


Metabolite - 4514
50
0.4309
0.146
17%


alpha-keto-glutarate
61
0.4325
0.1461
56%


Metabolite - 5211
50
0.4333
0.1461
−47%


cytidine
61
0.4411
0.1482
39%


Isobar-30-includes-maltotetraose-stachyose
61
0.4415
0.1482
−24%


Metabolite - 2198
61
0.4438
0.1486
−14%


Metabolite - 2389
61
0.447
0.1493
−10%


histamine
61
0.4668
0.1556
−12%


Metabolite - 3952
61
0.4773
0.1584
−19%


ascorbic acid
50
0.4775
0.1584
31%


Metabolite - 3694
61
0.4868
0.1611
−28%


Isobar-17-includes-arginine-N-alpha-acetyl-
61
0.4925
0.1625
−15%


ornithine


Metabolite - 1187
61
0.4931
0.1625
−24%


Metabolite - 4931
61
0.4969
0.1633
16%


Metabolite - 2319
61
0.5011
0.1643
−27%


Metabolite - 3189
61
0.5094
0.1667
39%


Metabolite - 3752
61
0.5167
0.1687
43%


Metabolite - 5215
50
0.5182
0.1688
−10%


Metabolite - 3484
61
0.5253
0.1707
32%


Metabolite - 3365
61
0.5283
0.171
−22%


Isobar-21-includes-gamma-aminobutyryl-L-
61
0.5285
0.171
−20%


histidine-L-anserine


Metabolite - 4272
50
0.5403
0.1742
−13%


Metabolite - 2185
61
0.5423
0.1742
19%


Metabolite - 3755
61
0.5431
0.1742
10%


Metabolite - 4497
50
0.5432
0.1742
−14%


orotidine-5-phosphate
61
0.5557
0.1777
−20%


Metabolite - 3051
61
0.5569
0.1777
26%


N-5-aminocarbonyl-L-ornithine
50
0.5705
0.1813
18%


Metabolite - 3317
61
0.5709
0.1813
19%


Metabolite - 2041
61
0.5719
0.1813
16%


Metabolite - 2846
61
0.5851
0.1844
−25%


cystine
50
0.5862
0.1844
−11%


Metabolite - 4032
50
0.5865
0.1844
26%


azelaic acid
61
0.5881
0.1844
16%


Metabolite - 3475
61
0.5881
0.1844
−17%


o-phosphoethanolamine
50
0.5905
0.1847
18%


cysteine
50
0.5935
0.1853
21%


Metabolite - 1911
61
0.5982
0.1861
22%


Metabolite - 4053
50
0.5988
0.1861
15%


galactose
50
0.6145
0.1906
−10%


Metabolite - 1183
61
0.6174
0.191
−22%


Metabolite - 2212
61
0.6301
0.1946
31%


hypotaurine
50
0.6325
0.1949
18%


Metabolite - 3957
61
0.6423
0.1975
11%


Metabolite - 1286
61
0.646
0.1982
−6%


Isobar-22-includes-glutamic acid-O-acetyl-L-
61
0.6499
0.199
6%


serine


Metabolite - 4616
61
0.6537
0.1997
−16%


Isobar-32-includes-N-acetyl-D-glucosamine-
61
0.659
0.2009
−8%


N-acetyl-D-mannosamine


Metabolite - 2407
61
0.6631
0.2017
−8%


N—N-dimethylarginine
61
0.6691
0.2031
13%


Metabolite - 4354
50
0.6766
0.2049
−8%


Metabolite - 4510
50
0.6881
0.2076
11%


tyramine
50
0.6893
0.2076
5%


Metabolite - 4632
50
0.6898
0.2076
6%


Metabolite - 4271
50
0.6928
0.2081
22%


Metabolite - 3994
61
0.6964
0.2087
−16%


Metabolite - 1085-possible-isolobinine-or-4-
61
0.6977
0.2087
−8%


aminoestra-1-3-5-10-triene-3-17beta-diol


Metabolite - 4448
61
0.7093
0.2117
−6%


Metabolite - 2064
61
0.7138
0.2126
7%


glutamine
50
0.7211
0.2143
12%


guanine
50
0.7322
0.2172
−14%


Metabolite - 2279
61
0.7424
0.2195
−10%


4-methyl-2-oxopentanoate
61
0.7432
0.2195
12%


Metabolite - 3040
50
0.7523
0.2217
−7%


Metabolite - 2691
61
0.7568
0.2226
11%


Isobar-18-includes-D-fructose-1-phosphate-
61
0.7623
0.2233
−9%


beta-D-fructose-6-phosphate


Metabolite - 4523
50
0.7627
0.2233
6%


Metabolite - 3027
50
0.7639
0.2233
10%


Metabolite - 4043
50
0.7735
0.2254
4%


dulcitol
50
0.7743
0.2254
−6%


beta-D-lactose
50
0.7821
0.2272
11%


Metabolite - 1975
61
0.7859
0.2279
11%


5-oxoproline
50
0.7882
0.2281
5%


Metabolite - 3813
61
0.7998
0.2306
14%


3-nitro-L-tyrosine
50
0.8003
0.2306
8%


Metabolite - 4002
50
0.815
0.2344
5%


Metabolite - 4238
61
0.8303
0.2383
8%


Metabolite - 2388
61
0.8374
0.2399
−4%


Metabolite - 3783
61
0.8416
0.2406
−6%


Metabolite - 4084
50
0.849
0.2422
1%


Metabolite - 3778
61
0.8508
0.2423
−8%


Metabolite - 3476
61
0.8527
0.2423
−6%


Metabolite - 1979-Cl-adduct-of-C6H10O5
61
0.8564
0.2426
−5%


Metabolite - 1980
61
0.8571
0.2426
9%


Metabolite - 2005
61
0.8602
0.243
5%


alpha-amino-adipate
50
0.862
0.243
7%


Metabolite - 5213
50
0.8674
0.2441
−4%


glucose-6-phosphate
50
0.8781
0.2461
−4%


Metabolite - 2174
61
0.8781
0.2461
5%


Metabolite - 5147
61
0.881
0.2464
−14%


Metabolite - 4020
50
0.8947
0.2493
3%


adenine
50
0.8948
0.2493
−4%


Metabolite - 3176-possible-creatine
61
0.9158
0.2547
−1%


Metabolite - 2180
61
0.937
0.26
3%


Metabolite - 3576
61
0.9487
0.2624
2%


2-deoxyuridine-5-triphosphate
61
0.9491
0.2624
−2%


L-histidinol
61
0.9545
0.2629
1%


Metabolite - 4096-gamma-glu-gly-leu-
61
0.9545
0.2629
−1%


Metabolite - 2753
61
0.9699
0.2664
1%


Isobar-31-includes-maltotriose-melezitose
61
0.9712
0.2664
1%


glucono-gamma-lactone
50
0.9791
0.2681
1%


uridine-5-monophosphate
61
0.9814
0.2682
0%


asparagine
50
0.9893
0.2695
0%


mannose
50
0.9898
0.2695
0%


2-deoxy-D-glucose
50
0.9996
0.2716
0%









Example 2
Cancer vs. Non-Cancer
Biomarkers were discovered by (1) analyzing plasma and/or urine samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
The plasma and/or urine samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer and 48 individuals with prostate cancer. After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Prostate cancer vs. Control plasma, Prostate cancer vs. Control urine).
Biomarkers:
As listed below in Table 4, biomarkers were discovered that were differentially present between plasma samples from subjects with prostate cancer and Control subjects with negative prostate biopsies (i.e. not diagnosed with prostate cancer). Table 5 lists biomarkers that were discovered that were differentially present between urine samples from subjects with prostate cancer and Control subjects (i.e. not diagnosed with prostate cancer).
Tables 4 and 5 include, for each listed biomarker, the p-value and the q-value determined in the statistical analysis of the data concerning the biomarkers and an indication of the percentage difference in the lower grade prostate cancer mean level as compared to the control mean level (Table 4) and the metastatic/high grade prostate cancer mean level as compared to the control mean level (Table 5). The term “Isobar” as used in the tables indicates the compounds that could not be distinguished from each other on the analytical platform used in the analysis (i.e., the compounds in an isobar elute at nearly the same time and have similar (and sometimes exactly the same) quant ions, and thus cannot be distinguished). Library indicates the chemical library that was used to identify the compounds. The number 50 refers to the GC library and the number 35 refers to the LC library.







TABLE 4







Prostate Cancer Biomarkers from Plasma from subjects with Prostate


Cancer compared to Plasma from Control subjects.















% Change


COMPOUND
Library
p-value
q-value
in PCA














Metabolite - 3377
35
0
0.0043
192%


Metabolite - 2329
35
1.00E−04
0.0144
73%


Metabolite - 3305
35
1.00E−04
0.0138
144%


palmitoleic acid
50
4.00E−04
0.0313
67%


Metabolite - 3327
35
5.00E−04
0.0313
111%


Metabolite - 1127
35
6.00E−04
0.0313
54%


DL-indole-3-lactic acid
50; 35
7.00E−04
0.0325
33%


Metabolite - 3322
35
8.00E−04
0.0325
84%


Metabolite - 1185
35
0.0012
0.045
−41%


elaidic acid
50
0.0021
0.0665
54%


Metabolite - 3603
35
0.0022
0.0665
−29%


lactate
50
0.0035
0.0882
17%


Metabolite - 2141
35
0.0036
0.0882
126%


Metabolite - 5349
50
0.0037
0.0882
−19%


Metabolite - 2711
35
0.0046
0.1028
27%


caffeine
35
0.0049
0.1041
104%


N-acetyl-L-valine
35
0.0061
0.1135
−18%


monosaccharide
50
0.0063
0.1135
−18%


Metabolite - 2108
35
0.0069
0.1135
65%


Metabolite - 3402
35
0.007
0.1135
59%


Metabolite - 2407
35
0.0071
0.1135
−34%


n-hexadecanoic acid
50
0.0078
0.1191
19%


Metabolite - 3030
50
0.0082
0.1196
−18%


Metabolite - 1988
35
0.01
0.1398
43%


alpha-keto-glutarate
35
0.0104
0.1398
81%


Metabolite - 1121
35
0.0123
0.1555
−24%


Isobar-17-includes-arginine-N-alpha-
35
0.0125
0.1555
−27%


acetyl-ornithine


Metabolite - 1104
35
0.0155
0.1863
20%


Metabolite - 1116
35
0.0183
0.2034
78%


Metabolite - 1286
35
0.0188
0.2034
−15%


Metabolite - 1713
35
0.0189
0.2034
54%


Metabolite - 3088
50
0.0199
0.2034
−30%


Metabolite - 3977
35
0.0207
0.2034
20%


theobromine-theophylline
35
0.0212
0.2034
74%


Metabolite - 1839
35
0.0223
0.2034
85%


valine
50
0.0224
0.2034
16%


tartaric acid
35
0.0225
0.2034
61%


Metabolite - 3033
50
0.0244
0.2034
−13%


Metabolite - 1085-possible-isolobinine-or-
35
0.0247
0.2034
−17%


4-aminoestra-1-3-5-10-triene-3-17beta-


diol


glycerol
50
0.0247
0.2034
16%


3-methylglutaric acid
35
0.0249
0.2034
22%


Metabolite - 1831-possible-Cl-adduct-of-
35
0.0253
0.2034
160%


citrulline


Metabolite - 3303
35
0.0278
0.2179
19%


Metabolite - 3900
35
0.0294
0.2256
16%


octadecanoic acid
50
0.0337
0.2512
11%


Metabolite - 3843
35
0.0346
0.2512
22%


Metabolite - 2978
50
0.035
0.2512
−22%


Metabolite - 2005
35
0.0359
0.252
35%


aspartate
50
0.041
0.2818
34%


3-hydroxybutanoic acid
50
0.0434
0.2924
81%


Metabolite - 3832-possible-phenol-sulfate
35
0.0475
0.314
97%


phenylalanine
35
0.05
0.3241
7%


Metabolite - 3040
50
0.0517
0.329
−21%


alpha-tocopherol
50
0.0529
0.3301
91%


Metabolite - 3002
50
0.0539
0.3305
27%


creatinine
35
0.0563
0.3392
11%


dethiobiotin
50; 35
0.0603
0.3565
30%


linoleic acid
50
0.0622
0.3598
17%


L-homoserine
50
0.063
0.3598
−16%


Metabolite - 3309
35
0.066
0.3707
37%


Metabolite - 4147
50
0.0676
0.3735
32%


3-chloro-L-tyrosine
50
0.0704
0.3747
23%


isoleucine
50
0.072
0.3747
15%


Metabolite - 1834
35
0.0729
0.3747
54%


Metabolite - 3781-possible-Na-adduct-of-
35
0.073
0.3747
−9%


Isobar-21


Metabolite - 2390
35
0.0735
0.3747
38%


3-amino-isobutyrate
50
0.0756
0.3747
−13%


Metabolite - 3098
50
0.0761
0.3747
−24%


Metabolite - 2389
35
0.0767
0.3747
−65%


Metabolite - 3178-possible-NH3-adduct-
35
0.0803
0.3786
16%


of-isobar-42


Metabolite - 4031-possible-
35
0.0804
0.3786
14%


norlevorphenol-isobutylphendienamide-


amprolium


alanine
50
0.0821
0.3786
18%


leucine
50
0.0833
0.3786
15%


Metabolite - 1817
35
0.084
0.3786
−20%


Metabolite - 3146
35
0.0842
0.3786
49%


Metabolite - 3830
35
0.0863
0.3791
31%


alpha-4-dihydroxybenzenepropanoic acid
50
0.0866
0.3791
36%


Metabolite - 1829
35
0.0881
0.3809
−13%


Metabolite - 3534
35
0.0918
0.3827
43%


Metabolite - 4511
50
0.0925
0.3827
37%


Metabolite - 2285
35
0.0932
0.3827
217%


D-quinic acid
50
0.094
0.3827
72%


Isobar-6-includes-valine-betaine
35
0.0949
0.3827
8%


Metabolite - 3707
35
0.0965
0.3827
−52%


Metabolite - 3837
35
0.0965
0.3827
30%


Metabolite - 3813
35
0.0991
0.3855
38%


Metabolite - 2130
35
0.1005
0.3855
−43%


Metabolite - 3014
50
0.1016
0.3855
19%


Metabolite - 1836
35
0.1036
0.3855
39%


tryptophan
50; 35
0.1049
0.3855
12%


Metabolite - 3772
35
0.1052
0.3855
16%


Metabolite - 3138
35
0.1056
0.3855
31%


4-methyl-2-oxopentanoate
50
0.1063
0.3855
20%


glycine
50
0.1082
0.386
19%


Metabolite - 3314
35
0.1088
0.386
28%


Metabolite - 2254
35
0.112
0.3897
70%


Metabolite - 2974
50
0.1132
0.3897
−13%


p-acetamidophenyl-beta-D-glucuronide
35
0.1133
0.3897
392%


Metabolite - 3489
35
0.1178
0.4011
54%


Metabolite - 4362
50
0.1232
0.4152
−19%


carnosine
35
0.1257
0.4163
24%


melatonin
50
0.1259
0.4163
−11%


Metabolite - 3758
35
0.1279
0.4163
62%


Metabolite - 1609
35
0.1285
0.4163
23%


Metabolite - 2698
35
0.1297
0.4163
42%


trans-4-hydroxyproline
35; 50
0.1352
0.4205
−22%


Metabolite - 2391
35
0.1363
0.4205
15%


Metabolite - 4769
50
0.1368
0.4205
−15%


Metabolite - 3074
50
0.1368
0.4205
70%


Metabolite - 3067
50
0.1372
0.4205
13%


adenosine-5-monophosphate
35
0.142
0.4314
22%


Metabolite - 2287
35
0.1436
0.4322
−78%


Metabolite - 2388
35
0.1466
0.4372
−10%


cholesterol
50
0.1481
0.4372
11%


Metabolite - 1975
35
0.15
0.4372
−35%


Metabolite - 3016
50
0.1504
0.4372
10%


heptanedioic acid
35
0.1522
0.4378
−33%


glyceric acid
50
0.1532
0.4378
−16%


Metabolite - 2506
35
0.1556
0.4395
63%


azelaic acid
35
0.1571
0.4395
12%


Metabolite - 3143
35
0.1583
0.4395
21%


Metabolite - 5419
50
0.159
0.4395
29%


Metabolite - 2867
35
0.1608
0.4408
100%


Metabolite - 2056
35
0.1623
0.4412
17%


Isobar-13-includes-5-keto-D-gluconic
35
0.1646
0.4439
24%


acid-2-keto-L-gulonic acid-D-glucuronic


acid


glutamic acid
50
0.1716
0.4557
22%


Metabolite - 2924
50
0.1732
0.4557
20%


Metabolite - 3073
50
0.1743
0.4557
−19%


Isobar-5-includes-asparagine-ornithine
35
0.1744
0.4557
−14%


benzoic acid
50; 35
0.176
0.4557
−19%


tyramine
50
0.1771
0.4557
14%


Metabolite - 2255
35
0.183
0.459
−58%


glucose-6-phosphate
50
0.1835
0.459
6%


Metabolite - 1977
35
0.1838
0.459
14%


Metabolite - 2316
35
0.1841
0.459
−36%


2-keto-L-gulonic acid
50
0.1863
0.459
5%


n-dodecanoate
50
0.187
0.459
14%


Metabolite - 3474
35
0.189
0.459
−19%


ornithine
50
0.1892
0.459
22%


L-beta-imidazolelactic acid
50; 35
0.1952
0.4677
10%


5-oxoproline
50
0.1956
0.4677
10%


carnitine
35
0.197
0.4678
−9%


glutamine
50
0.1993
0.4698
16%


Metabolite - 3216
35
0.2052
0.4785
21%


Metabolite - 2212
35
0.2067
0.4785
−17%


fructose
50
0.2072
0.4785
29%


Metabolite - 3091
50
0.2097
0.481
−32%


Metabolite - 3109
50
0.216
0.4901
−25%


Metabolite - 2507
35
0.2166
0.4901
54%


histidine
50
0.2197
0.4937
13%


Metabolite - 5403
50
0.2235
0.4991
−11%


Metabolite - 1113-possible-
35
0.2254
0.5
14%


acetylcarnitine-or-isopentyl-adenine


catechol
35
0.2295
0.5058
53%


Metabolite - 3019
50
0.232
0.508
−10%


Metabolite - 4032
50
0.2399
0.5217
23%


Metabolite - 2898
35
0.2417
0.5223
57%


Metabolite - 3017
50
0.2449
0.5245
−13%


5-6-Dimethylbenzimidazole
50
0.2458
0.5245
25%


Metabolite - 1211
35
0.2482
0.5261
−67%


Metabolite - 2111
35
0.2497
0.5261
25%


Metabolite - 3160
35
0.2544
0.5298
18%


Metabolite - 4767
50
0.2546
0.5298
−19%


threonine
50
0.2588
0.5353
9%


Metabolite - 4042
50
0.2647
0.5433
8%


Metabolite - 2269-
35
0.2698
0.5433
−25%


Metabolite - 4078
35
0.2704
0.5433
23%


Metabolite - 3215
35
0.2706
0.5433
15%


Metabolite - 3624
35
0.2708
0.5433
23%


Metabolite - 3085
50
0.2758
0.5438
13%


Metabolite - 2914
50
0.2774
0.5438
−2%


Metabolite - 1110
35
0.2792
0.5438
−31%


Metabolite - 4167
35
0.2792
0.5438
20%


Metabolite - 3752
35
0.282
0.5438
−60%


Metabolite - 3877
35
0.2832
0.5438
28%


Metabolite - 3165
35
0.2842
0.5438
7%


glucono-gamma-lactone
50
0.2848
0.5438
7%


Metabolite - 3578
35
0.2855
0.5438
−24%


Metabolite - 3102
50
0.2897
0.5449
9%


Metabolite - 3131
35
0.2901
0.5449
−23%


Metabolite - 2027
35
0.2909
0.5449
18%


Metabolite - 3972
35
0.2949
0.5488
−13%


Metabolite - 1188
35
0.3012
0.5488
−17%


Metabolite - 2279
35
0.3017
0.5488
36%


arachidonic acid
50
0.304
0.5488
16%


Metabolite - 3089
50
0.3056
0.5488
23%


DL-cystathionine
35
0.3083
0.5488
−11%


trans-2-3-4-trimethoxycinnamic acid
35
0.3128
0.5488
−26%


p-hydroxybenzaldehyde
35
0.3129
0.5488
10%


Metabolite - 3576
35
0.3151
0.5488
−17%


Metabolite - 5489
50
0.3161
0.5488
−9%


Metabolite - 4795
50
0.3168
0.5488
−18%


Metabolite - 4504
50
0.3207
0.5488
16%


Metabolite - 3025
50
0.321
0.5488
−9%


fumaric acid
50
0.3213
0.5488
12%


Isobar-36-includes-D-sorbitol-6-
35
0.3219
0.5488
16%


phosphate-mannitol-1-phosphate


Metabolite - 1203-possible-
35
0.3221
0.5488
33%


acetylbrowniine-tricornine-germine-or-


veracevine


Metabolite - 3023
50
0.3225
0.5488
−9%


xylitol
35; 50
0.3244
0.5488
−16%


Metabolite - 2592
35
0.3264
0.5488
71%


methyl-indole-3-acetate
35
0.3269
0.5488
14%


Metabolite - 3313
35
0.3272
0.5488
61%


Metabolite - 1498
35
0.3289
0.549
−13%


Metabolite - 3184
35
0.3345
0.5509
15%


serine
50
0.3365
0.5509
7%


succinate
50
0.3397
0.5509
−7%


GABA
50
0.3397
0.5509
12%


Metabolite - 3027
50
0.3399
0.5509
−8%


Metabolite - 1656
35
0.341
0.5509
−14%


Metabolite - 3086
50
0.3429
0.5509
−19%


malic acid
35
0.3478
0.5509
26%


Metabolite - 4196
50
0.3484
0.5509
26%


Metabolite - 5906
50
0.3494
0.5509
35%


allantoin
35
0.351
0.5509
9%


L-alpha-glycerophosphorylcholine
35
0.3514
0.5509
22%


L-allo-threonine
50
0.3516
0.5509
7%


Metabolite - 2347
35
0.3533
0.5509
−23%


3-methyl-L-histidine
35
0.3568
0.5509
6%


Metabolite - 1914
35
0.3578
0.5509
−25%


3-phospho-d-glycerate
35
0.3582
0.5509
16%


Isobar-20-includes-fumaric acid-3-methyl-
35
0.3628
0.5509
−17%


2-oxobutanoate


urea
50
0.3643
0.5509
−6%


4-hydroxyphenylacetate
35; 50
0.3644
0.5509
5%


Metabolite - 4611
50
0.3655
0.5509
7%


Metabolite - 3807
35
0.366
0.5509
5%


pyridoxal-phosphate
35
0.3699
0.5528
−4%


Metabolite - 4361
50
0.3706
0.5528
−15%


adonitol
50
0.3737
0.5551
5%


N-N-dimethylarginine
35
0.3769
0.5553
9%


pantothenic acid
35
0.3772
0.5553
20%


Metabolite - 3012
50
0.384
0.5609
−7%


DL-pipecolic acid
35
0.3851
0.5609
11%


Isobar-4-includes-Gluconic acid-DL-
35
0.3861
0.5609
−12%


arabinose-D-ribose-L-xylose-DL-lyxose-


D-xylulose


Metabolite - 4355
50
0.389
0.5609
24%


DL-homocysteine
35
0.3893
0.5609
13%


25-hydroxycholesterol
50
0.3953
0.5642
4%


Metabolite - 4272
50
0.3955
0.5642
13%


Metabolite - 3130
35
0.3968
0.5642
18%


diaminopimelic acid
50; 35
0.3989
0.5642
−8%


Metabolite - 1835
35
0.4018
0.5642
−11%


Metabolite - 2281
35
0.403
0.5642
39%


Metabolite - 3498
35
0.4042
0.5642
−9%


Metabolite - 4084
50
0.405
0.5642
22%


proline
35; 50
0.4097
0.5684
8%


Metabolite - 3058
50
0.4147
0.573
−13%


Metabolite - 2888-possible-sulfated-
35
0.4195
0.5751
−11%


Rosiglitazone


Metabolite - 3078
50
0.4196
0.5751
−8%


Metabolite - 1911
35
0.4221
0.5761
−20%


inositol
50
0.4245
0.577
5%


citrulline
50
0.428
0.5795
−6%


Metabolite - 3055-possible-NH3-adduct-
35
0.4333
0.5828
−19%


of-hippuric acid


Metabolite - 4134
50
0.4339
0.5828
−6%


Metabolite - 2546
35
0.4358
0.583
15%


mannose
50
0.4399
0.5862
4%


Metabolite - 4516
50
0.4457
0.5899
−6%


Metabolite - 5437
50
0.4462
0.5899
27%


Metabolite - 3955
35
0.4482
0.5902
−23%


phosphoenolpyruvate
35
0.453
0.5922
10%


Metabolite - 4234
35
0.4546
0.5922
9%


Metabolite - 5847
50
0.455
0.5922
20%


citric acid
50
0.4573
0.5922
4%


Metabolite - 2915
50
0.4585
0.5922
−6%


Metabolite - 3125
35
0.4693
0.6021
7%


Metabolite - 3081
50
0.4697
0.6021
9%


Metabolite - 3370
35
0.4719
0.6026
9%


Metabolite - 4096-possible-gamma-glu-
35
0.4808
0.6117
−16%


gly-leu-


4-amino-5-methyl-2-1H-pyrimidinone
35
0.4852
0.6129
9%


Metabolite - 5427
50
0.4874
0.6129
4%


Metabolite - 4163
35
0.4882
0.6129
13%


Metabolite - 1216
35
0.489
0.6129
8%


nonanate
50
0.4925
0.6137
−3%


oxitryptan
35
0.4933
0.6137
10%


Metabolite - 2139
35
0.4964
0.6153
−8%


methionine
35
0.499
0.6163
4%


Metabolite - 3783
35
0.5036
0.6193
−11%


galactose
50
0.5059
0.6193
−6%


sn-Glycerol-3-phosphate
50
0.5069
0.6193
5%


Metabolite - 1208
35
0.5108
0.6218
19%


Metabolite - 2250
35
0.5155
0.6239
−15%


dulcitol
50
0.5164
0.6239
−6%


Metabolite - 4133
50
0.5194
0.6239
−7%


Metabolite - 2849-related-to-citric acid-
35
0.52
0.6239
−6%


dopamine
50
0.5264
0.6251
13%


Metabolite - 2386
35
0.5265
0.6251
17%


Metabolite - 4986
50
0.5287
0.6251
−14%


Metabolite - 3044
35
0.5288
0.6251
9%


Metabolite - 3094
50
0.5302
0.6251
7%


Metabolite - 2387
35
0.5328
0.6256
49%


gamma-L-glutamyl-L-tyrosine
35
0.5344
0.6256
−4%


Isobar-2-includes-3-amino-isobutyrate-2-
35
0.5412
0.6289
18%


amino-butyrate-4-aminobutanoic acid-


dimethylglycine-choline-


L-homoserine-lactone
35
0.5419
0.6289
−13%


Isobar-19-includes-D-saccharic acid-2-
35
0.5463
0.6289
−10%


deoxy-D-galactose-2-deoxy-D-glucose-L-


fucose-L-rhamnose


gamma-L-glutamyl-L-glutamine
35
0.5465
0.6289
−11%


Metabolite - 2567
35
0.5492
0.6289
−6%


Metabolite - 1086
35
0.5505
0.6289
11%


Metabolite - 4275
50
0.5511
0.6289
−6%


Metabolite - 3077
50
0.5522
0.6289
−6%


gamma-glu-leu
35
0.5551
0.6291
5%


Metabolite - 3320-possible-pimpinellin-or-
35
0.5561
0.6291
27%


tetrahydroxybenzophenone


Metabolite - 3992-possible-Cl-adduct-of-
35
0.56
0.6314
−4%


Formate-dimer


Metabolite - 1389-possible-glucuronide-
35
0.5643
0.6335
14%


form-of-Metabolite - 1359


Metabolite - 3020
50
0.5697
0.6335
−6%


guanosine-5-diphosphate
35
0.5698
0.6335
9%


Metabolite - 3426
35
0.5712
0.6335
2%


Metabolite - 2185
35
0.5746
0.6335
−5%


orotidine-5-phosphate
35
0.5748
0.6335
12%


Metabolite - 3951
35
0.575
0.6335
5%


biliverdin
35
0.5834
0.6407
9%


Metabolite - 2313
35
0.5904
0.6449
7%


Metabolite - 3056
35
0.5918
0.6449
5%


normetanephrine
50
0.593
0.6449
−6%


Metabolite - 2100
35
0.6011
0.6511
−4%


tyrosine
50
0.6026
0.6511
4%


Metabolite - 1142-possible-5-
35
0.611
0.6582
12%


hydroxypentanoate-or-beta-


hydroxyisovaleric acid


Metabolite - 1597
35
0.6293
0.6744
−3%


Metabolite - 3441
35
0.6319
0.6744
6%


glycochenodeoxycholic
35
0.6334
0.6744
14%


acid/glycodeoxycholic acid


Metabolite - 5346
50
0.6341
0.6744
5%


Metabolite - 3765
35
0.6389
0.6774
12%


Metabolite - 2249
35
0.6409
0.6774
7%


Metabolite - 4593
50
0.6542
0.6824
−2%


hippuric acid
35
0.6581
0.6824
10%


Metabolite - 3022
50
0.6591
0.6824
−5%


niacinamide
35
0.6593
0.6824
11%


phytonadione
50
0.6599
0.6824
4%


5-methoxytryptamine
50
0.6645
0.6824
−6%


Metabolite - 2486
35
0.6655
0.6824
9%


N-6-trimethyl-l-lysine
35
0.6657
0.6824
6%


Metabolite - 2753
35
0.6692
0.6824
5%


Metabolite - 3670
35
0.6697
0.6824
4%


Metabolite - 1465
35
0.67
0.6824
6%


Metabolite - 3604
35
0.6701
0.6824
−11%


Metabolite - 3075
50
0.6739
0.6824
−6%


Metabolite - 3879
35
0.6755
0.6824
−20%


Metabolite - 4148
50
0.6761
0.6824
−7%


Isobar-21-includes-gamma-aminobutyryl-
35
0.6781
0.6824
−7%


L-histidine-L-anserine


N-acetyl-L-leucine
35
0.6834
0.6858
13%


D-allose
50
0.6934
0.6906
−5%


Metabolite - 3181
35
0.6944
0.6906
5%


Metabolite - 3099
50
0.697
0.6906
8%


Metabolite - 2688
35
0.6986
0.6906
−8%


3-nitro-L-tyrosine
50; 35
0.7005
0.6906
8%


Metabolite - 3653-Possible-stachydrine-
35
0.7021
0.6906
−12%


Metabolite - 2392
35
0.7026
0.6906
18%


Metabolite - 3132
35
0.7104
0.695
3%


Isobar-25-includes-L-gulono-1-4-lactone-
35
0.7112
0.695
8%


glucono-gamma-lactone-


Metabolite - 1323-possible-4-sulfobenzyl-
35
0.7154
0.6971
3%


alcohol


heneicosanoic acid-methyl-ester
50
0.7198
0.6975
−4%


guanidineacetic acid
35
0.7202
0.6975
−5%


Metabolite - 1215
35
0.7223
0.6975
−11%


hypoxanthine
35
0.7241
0.6975
5%


Metabolite - 3134
35
0.7323
0.7008
13%


Isobar-30-includes-maltotetraose-
35
0.7345
0.7008
5%


stachyose


Metabolite - 2853
35
0.7345
0.7008
7%


Metabolite - 1244
35
0.7359
0.7008
6%


Metabolite - 1342-possible-
35
0.7405
0.7032
−7%


phenylacetylglutamine-or-formyl-N-acetyl-


5-methoxykynurenamine


Metabolite - 3135
35
0.7437
0.7043
−11%


pyrophosphate
35; 50
0.7499
0.7082
9%


ethyl-3-indoleacetate
50
0.7704
0.7186
3%


Metabolite - 3476
35
0.7739
0.7186
7%


Metabolite - 1183
35
0.778
0.7186
−8%


Isobar-9-includes-sucrose-beta-D-lactose-
35
0.7787
0.7186
5%


D-trehalose-D-cellobiose-D-Maltose-


palatinose-melibiose-alpha-D-lactose


Metabolite - 4503
50
0.7819
0.7186
9%


L-kynurenine
35
0.7838
0.7186
3%


Metabolite - 3093
50
0.7844
0.7186
6%


Metabolite - 4365
50
0.7869
0.7186
5%


Metabolite - 3698
35
0.7885
0.7186
6%


oxalacetic acid
35
0.7896
0.7186
5%


inosine
35
0.7915
0.7186
−9%


Metabolite - 1573
35
0.7953
0.7186
5%


uric acid
35
0.7956
0.7186
1%


vitamin-B6
50
0.7962
0.7186
2%


Metabolite - 4020
50
0.7967
0.7186
1%


Metabolite - 1351
35
0.7988
0.7186
3%


alphahydroxybenzeneacetic acid
35
0.8012
0.7186
−3%


Metabolite - 1915
35
0.8026
0.7186
−13%


Metabolite - 3994
35
0.8031
0.7186
7%


Metabolite - 3218
35
0.8059
0.7186
4%


phenyl-beta-glucopyranoside
50
0.8076
0.7186
−4%


Metabolite - 1289
35
0.8079
0.7186
5%


histamine
35
0.81
0.7186
−5%


Metabolite - 2370
35
0.8174
0.7197
−4%


Metabolite - 2053
35
0.818
0.7197
4%


Metabolite - 5907
50
0.8229
0.7197
−2%


hydroxyacetic acid
50
0.8232
0.7197
−4%


maltose
50
0.8234
0.7197
−4%


Metabolite - 3761
35
0.824
0.7197
5%


tryptamine
50
0.8298
0.7229
−3%


Metabolite - 2809
35
0.8365
0.7257
5%


Metabolite - 4768
50
0.8383
0.7257
6%


Metabolite - 2256
35
0.8395
0.7257
4%


Metabolite - 2973
50
0.8416
0.7257
−1%


Metabolite - 3245
35
0.8492
0.7286
4%


Metabolite - 2129
35
0.8493
0.7286
5%


Metabolite - 4274
50
0.8535
0.7303
2%


Metabolite - 1974
35
0.8572
0.7316
−4%


Metabolite - 1220
35
0.8619
0.7331
−5%


pyridoxamine-phosphate
35
0.8654
0.7331
−2%


thyroxine
35
0.8659
0.7331
−2%


N-acetylserotonin
50
0.868
0.7331
1%


Metabolite - 3968
35
0.8698
0.7331
4%


Metabolite - 3108
50
0.8722
0.7333
−1%


Metabolite - 2055
35
0.8779
0.7362
−2%


D-alanyl-D-alanine
35
0.8819
0.7378
2%


Metabolite - 4791
50
0.8875
0.7401
5%


Metabolite - 3816
35
0.8926
0.7401
2%


Metabolite - 3167
35
0.8948
0.7401
3%


4-Guanidinobutanoic acid
35
0.895
0.7401
2%


glycocholic acid
35
0.8957
0.7401
5%


Isobar-1-includes-mannose-fructose-
35
0.8978
0.7401
2%


glucose-galactose-alpha-L-


sorbopyranose-Inositol-D-allose


3-hydroxyphenylacetate
35
0.9038
0.7415
1%


Metabolite - 3004
50
0.9114
0.7415
2%


noradrenaline
50
0.9121
0.7415
2%


Metabolite - 2074
35
0.9154
0.7415
−2%


Metabolite - 2686
35
0.9155
0.7415
−1%


Metabolite - 3436
35
0.916
0.7415
−2%


Metabolite - 4091-possible-gamma-
35
0.9173
0.7415
1%


glutamyl-glutamic acid


3-methoxy-L-tyrosine
50
0.9174
0.7415
0%


7-8-dihydrofolic acid
35
0.9197
0.7415
−4%


Metabolite - 4238
35
0.9224
0.7415
−2%


glucarate
50
0.9243
0.7415
2%


phosphate
50
0.9259
0.7415
1%


Metabolite - 1979-Cl-adduct-of-C6H10O5
35
0.9351
0.7426
−1%


Metabolite - 1335
35
0.9375
0.7426
−1%


Metabolite - 3166
35
0.9387
0.7426
2%


xanthine
35
0.9416
0.7426
−2%


3-hydroxypropanoate
50
0.9424
0.7426
1%


Metabolite - 4015
50
0.9455
0.7426
0%


Metabolite - 3183-possible-gamma-L-
35
0.946
0.7426
−1%


glutamyl-L-phenylalanine-or-aspartame


Metabolite - 1111-possible-
35
0.9467
0.7426
−1%


methylnitronitrosoguanidine-or-ethyl-


thiocarbamoylacetate


Metabolite - 1843
35
0.9471
0.7426
−1%


Metabolite - 3615
35
0.9529
0.7437
−1%


octopamine
50
0.9564
0.7447
1%


Isobar-18-includes-D-fructose-1-
35
0.9652
0.7498
0%


phosphate-beta-D-fructose-6-phosphate


Metabolite - 3003
50
0.9736
0.7546
0%


Metabolite - 5366
50
0.983
0.757
0%


Metabolite - 4360
50
0.9831
0.757
−1%


Metabolite - 3097
50
0.9839
0.757
−1%


Metabolite - 1392
35
0.9857
0.757
1%


Metabolite - 3129
35
0.9973
0.7602
0%


Metabolite - 1133-possible-Na-adduct-of-
35
0.9981
0.7602
0%


EDTA


Metabolite - 3243
35
0.9986
0.7602
0%


Metabolite - 1349
35
0.9989
0.7602
0%
















TABLE 5







Prostate Cancer Biomarkers from Urine from subjects with Prostate


Cancer compared to Urine from Control subjects.















%


COMPOUND
Library
p-value
q-value
Change in PCA














Metabolite - 2974
50
0.0023
0.1555
−32%


2-amino-butyrate
50
0.0035
0.1555
−27%


guanidineacetic acid
35
0.0048
0.1555
−65%


citrulline
50
0.006
0.1555
−43%


Metabolite - 2752
35
0.0063
0.1555
−38%


adenosine
35
0.0067
0.1555
−46%


Metabolite - 2242
35
0.0068
0.1555
170%


3-methoxy-4-hydroxyphenylacetate
50
0.0096
0.1555
−41%


Metabolite - 4504
50
0.0118
0.1555
−36%


N-acetyl-D-glucosamine
50
0.012
0.1555
−53%


Metabolite - 2978
50
0.012
0.1555
−29%


Metabolite - 1573
35
0.013
0.1555
−28%


Metabolite - 2181
35
0.0134
0.1555
−34%


Metabolite - 4522
50
0.0149
0.1555
−35%


serine
50
0.016
0.1555
−38%


methionine
35
0.0162
0.1555
−32%


catechol
35
0.0163
0.1555
−60%


Metabolite - 3215
35
0.0164
0.1555
−31%


Metabolite - 4593
50
0.0167
0.1555
−36%


Isobar-9-includes-sucrose-beta-D-
35
0.017
0.1555
−49%


lactose-D-trehalose-D-cellobiose-D-


Maltose-palatinose-melibiose-alpha-D-


lactose


Metabolite - 2567
35
0.0188
0.1611
−33%


uracil
50
0.0194
0.1611
−36%


Metabolite - 3020
50
0.0217
0.1611
−41%


Metabolite - 3807
35
0.0225
0.1611
−25%


arabinose
50
0.0227
0.1611
−47%


histamine
35
0.0249
0.1611
−37%


Metabolite - 3761
35
0.026
0.1611
−31%


Metabolite - 3443
35
0.0262
0.1611
100%


DL-homocysteine
35
0.0263
0.1611
−43%


Metabolite - 2271
35
0.0264
0.1611
−47%


Metabolite - 4503
50
0.0264
0.1611
−38%


glycine
50
0.0284
0.1641
−37%


Isobar-4-includes-Gluconic acid-DL-
35
0.0297
0.1641
−33%


arabinose-D-ribose-L-xylose-DL-lyxose-


D-xylulose


adenosine-3-5-cyclic-monophosphate
35
0.0301
0.1641
−24%


citric acid
50
0.0304
0.1641
−38%


dopamine
50
0.0317
0.1641
−30%


Metabolite - 1974
35
0.0347
0.1641
−42%


N-acetylneuraminate
50
0.0348
0.1641
−32%


Metabolite - 3381
35
0.0352
0.1641
−35%


adenine
50
0.0359
0.1641
−37%


Metabolite - 2051
35
0.0361
0.1641
−22%


serotonin
35
0.0364
0.1641
−33%


Metabolite - 4636
50
0.0396
0.1641
−44%


Isobar-19-includes-D-saccharic acid-2-
35
0.0416
0.1641
−58%


deoxy-D-galactose-2-deoxy-D-glucose-


L-fucose-L-rhamnose


L-allo-threonine
50
0.0421
0.1641
−31%


Metabolite - 1349
35
0.0426
0.1641
−36%


N-6-trimethyl-l-lysine
35
0.0433
0.1641
−38%


Metabolite - 3370
35
0.0481
0.1641
−35%


Metabolite - 3056
35
0.0489
0.1641
−29%


Metabolite - 3803
35
0.049
0.1641
−41%


1-methyladenosine
35
0.0501
0.1641
−34%


N-tigloylglycine
35
0.0501
0.1641
−31%


tyrosine
50
0.0503
0.1641
−31%


threonine
50
0.0516
0.1641
−31%


Metabolite - 3951
35
0.0518
0.1641
−25%


carnosine
35
0.0542
0.1641
−37%


xylitol
35; 50
0.055
0.1641
−35%


caffeine
35
0.0555
0.1641
79%


Metabolite - 2277
35
0.0558
0.1641
−28%


Metabolite - 1979-Cl-adduct-of-
35
0.0565
0.1641
−45%


C6H10O5


heptanedioic acid
35
0.0573
0.1641
−28%


orotic acid
50
0.0584
0.1641
−44%


Metabolite - 1342-possible-
35
0.0596
0.1641
−29%


phenylacetylglutamine-or-formyl-N-


acetyl-5-methoxykynurenamine


beta-hydroxyisovaleric acid
50
0.0598
0.1641
−34%


Metabolite - 1911
35
0.0613
0.1641
−50%


ornithine
50
0.0615
0.1641
−34%


Metabolite - 4499
50
0.0619
0.1641
−36%


Metabolite - 4519
50
0.0619
0.1641
−55%


Metabolite - 2390
35
0.0635
0.1641
−43%


Metabolite - 3329
35
0.064
0.1641
−59%


7-8-dihydrofolic acid
35
0.0648
0.1641
−26%


Metabolite - 4251
50
0.0652
0.1641
−40%


Metabolite - 1655
35
0.0659
0.1641
−51%


Metabolite - 3955
35
0.0663
0.1641
−43%


N-acetyl-L-valine
35
0.0669
0.1641
−51%


3-ureidopropionic acid
35
0.0672
0.1641
−49%


erythrose-4-phosphate
50
0.0681
0.1641
−45%


Metabolite - 3033
50
0.0691
0.1641
−35%


gluconic acid
50
0.0697
0.1641
−46%


succinate
50
0.0704
0.1641
−41%


2-acetamido-1-amino-1-2-dideoxy-beta-
50
0.0705
0.1641
−36%


D-glucopyranose


fructose
50
0.072
0.1641
−43%


Metabolite - 3327
35
0.0729
0.1641
−46%


5-6-Dihydrothymine
35
0.0731
0.1641
−34%


Metabolite - 3908
35
0.0744
0.1641
−39%


Metabolite - 3305
35
0.0747
0.1641
−43%


Metabolite - 4502
50
0.0748
0.1641
−5%


phenylalanine
35
0.0753
0.1641
−25%


Metabolite - 3055-possible-NH3-adduct-
35
0.0765
0.1641
46%


of-hippuric acid


pyrophosphate
35; 50
0.0783
0.1641
−53%


Metabolite - 3183-possible-gamma-L-
35
0.079
0.1641
−37%


glutamyl-L-phenylalanine-or-aspartame


guanine
35
0.0803
0.1641
−30%


Metabolite - 3970
35
0.0804
0.1641
−31%


Metabolite - 3246-possible-Ala-GLy-
35
0.0816
0.1641
−38%


glycyl-sarcosine-or-ureido-butyric acid


5-6-Dimethylbenzimidazole
50
0.0818
0.1641
−47%


urocanic acid
35
0.0821
0.1641
−35%


Metabolite - 3813
35
0.083
0.1641
−32%


Metabolite - 4523
50
0.0831
0.1641
−30%


Metabolite - 2285
35
0.084
0.1641
−34%


5-hydroxyindoleacetate
50
0.0847
0.1641
−35%


Isobar-29-includes-R—S-hydroorotic
35
0.0847
0.1641
−81%


acid-5-6-dihydroorotic acid


valine
50
0.0849
0.1641
−23%


leucine
50
0.0862
0.1651
−37%


Metabolite - 4639
50
0.0905
0.1703
−52%


4-hydroxy-3-methoxymandelate
50
0.0906
0.1703
−33%


Metabolite - 1656
35
0.0927
0.1726
−52%


Metabolite - 2781
35
0.0965
0.1752
−22%


3-phospho-d-glycerate
35
0.0989
0.1752
−33%


N-acetyl-L-leucine
35
0.099
0.1752
−33%


Metabolite - 4505
50
0.0997
0.1752
−49%


Metabolite - 4002
50
0.0999
0.1752
−35%


Metabolite - 4112
35
0.1002
0.1752
−33%


4-acetominophen-sulfate
35
0.1013
0.1755
−35%


cellobiose
50
0.1027
0.1765
−48%


Metabolite - 1829
35
0.1037
0.1767
−22%


Metabolite - 3489
35
0.1062
0.1794
102%


DL-beta-hydroxyphenylethylamine
35
0.1082
0.1813
−29%


Metabolite - 4628
50
0.1098
0.182
−57%


4-hydroxymandelate
50
0.1115
0.182
−39%


5-oxoproline
50
0.1124
0.182
−29%


4-acetamidobutyric acid
35
0.1142
0.182
−28%


4-Guanidinobutanoic acid
35
0.1143
0.182
−28%


Metabolite - 2546
35
0.1157
0.182
−23%


histidine
50
0.1191
0.182
−38%


cysteine
50
0.1196
0.182
−52%


Metabolite - 4516
50
0.1197
0.182
−53%


L-beta-imidazolelactic acid
50; 35
0.1201
0.182
−25%


Metabolite - 2293-possible-O-
35
0.1215
0.182
−32%


desmethylvenlafaxine-glucuronide


Metabolite - 1383-possible-salicyluric-
35
0.1218
0.182
−52%


glucuronide


Metabolite - 4027
50
0.1224
0.182
−28%


Metabolite - 2807
35
0.1228
0.182
−44%


Metabolite - 3576
35
0.1229
0.182
−44%


cis-aconitic acid
50
0.124
0.182
−43%


Metabolite - 3322
35
0.1266
0.182
−39%


N—N-dimethylarginine
35
0.1269
0.182
−23%


Metabolite - 3828
35
0.1273
0.182
−32%


noradrenaline
50
0.1276
0.182
−43%


Metabolite - 4638
50
0.1281
0.182
−49%


creatinine
35
0.1327
0.1866
−17%


Metabolite - 4618
50
0.1343
0.1868
−32%


Metabolite - 4629
50
0.1347
0.1868
−31%


Metabolite - 3800
35
0.1366
0.1881
−40%


3-hydroxybutanoic acid
50
0.1415
0.1926
92%


Metabolite - 3817
35
0.1418
0.1926
−30%


methylmalonic acid
50
0.143
0.193
−42%


Metabolite - 4595
50
0.1443
0.1932
−23%


Metabolite - 4637
50
0.1468
0.1932
−54%


Metabolite - 3830
35
0.1474
0.1932
−40%


Metabolite - 4624
50
0.1475
0.1932
−24%


xanthine
35
0.148
0.1932
−43%


Metabolite - 3805
35
0.1504
0.195
−26%


Metabolite - 4635
50
0.1599
0.1957
−56%


folic acid
35
0.1603
0.1957
−37%


diaminopimelic acid
50; 35
0.1608
0.1957
−26%


Metabolite - 2973
50
0.1618
0.1957
29%


Metabolite - 3973
35
0.1629
0.1957
−65%


Metabolite - 3605
35
0.163
0.1957
−44%


N-formyl-L-methionine
35
0.1643
0.1957
−35%


urea
50
0.1643
0.1957
−21%


riboflavine
35
0.1654
0.1957
−73%


Metabolite - 1289
35
0.1665
0.1957
−16%


Metabolite - 3380
35
0.1674
0.1957
−29%


Metabolite - 4611
50
0.1674
0.1957
−26%


Metabolite - 4511
50
0.1685
0.1957
−38%


(1′R-1′S)_biopterin
35
0.1687
0.1957
−25%


1-methyladenine
50
0.1694
0.1957
−45%


4-hydroxy-2-quinolinecarboxylic acid
50
0.17
0.1957
−41%


Metabolite - 3994
35
0.1716
0.1957
−32%


Metabolite - 2550
35
0.1717
0.1957
−44%


Metabolite - 3898
35
0.1721
0.1957
−16%


Metabolite - 3103
50
0.1723
0.1957
43%


possible-L-homocysteine-thiolactone-
50
0.1735
0.1959
−30%


identical-to-homocysteine


Metabolite - 1122
35
0.1757
0.1972
−23%


tryptophan
50; 35
0.1769
0.1972
−20%


Metabolite - 1335
35
0.1775
0.1972
−23%


Metabolite - 2557-possible-
35
0.1812
0.2002
−34%


Pantoprazole-metabolite


asparagine
50
0.1833
0.2014
−32%


Metabolite - 3837
35
0.1862
0.2025
−33%


Metabolite - 3659
35
0.1878
0.2025
−26%


mannitol
50
0.1883
0.2025
−39%


D-alanyl-D-alanine
35
0.1885
0.2025
−23%


3-amino-isobutyrate
50
0.1894
0.2025
−39%


Metabolite - 4498
50
0.1936
0.2059
−27%


hypoxanthine
35
0.1978
0.2093
−36%


Isobar-24-includes-L-arabitol-adonitol
35
0.2001
0.2095
−8%


hydroxyacetic acid
50
0.2012
0.2095
−21%


Metabolite - 1843
35
0.2013
0.2095
−18%


Metabolite - 3216
35
0.2022
0.2095
−8%


Metabolite - 2175
35
0.2045
0.2108
−49%


alanine
50
0.2058
0.211
−27%


Metabolite - 2366
35
0.2076
0.2118
40%


Metabolite - 3873
35
0.2143
0.2124
−23%


Metabolite - 4046
50
0.2165
0.2124
−73%


Metabolite - 1455
35
0.2166
0.2124
−18%


Metabolite - 3708
35
0.2167
0.2124
−63%


Metabolite - 3843
35
0.217
0.2124
−30%


Metabolite - 3886
35
0.2177
0.2124
−21%


Metabolite - 2174
35
0.2178
0.2124
−23%


4-8-dihydroxyquinoline-2-carboxylic
50
0.2182
0.2124
−31%


acid


Metabolite - 3387
35
0.2183
0.2124
−23%


Metabolite - 4271
50
0.2193
0.2124
−30%


tyramine
50
0.2204
0.2124
−42%


Metabolite - 4496
50
0.2215
0.2124
−15%


normetanephrine
50
0.2223
0.2124
−13%


Metabolite - 1679
35
0.2229
0.2124
−22%


trans-4-hydroxyproline
35; 50
0.2281
0.2163
−24%


Metabolite - 2703
35
0.2307
0.2174
−14%


Metabolite - 3169
35
0.2314
0.2174
−62%


Metabolite - 4634
50
0.2337
0.2185
−28%


Metabolite - 3221
35
0.2367
0.2196
−25%


alpha-4-dihydroxybenzenepropanoic
50
0.237
0.2196
−48%


acid


uric acid
35
0.243
0.2227
−6%


Metabolite - 3841
35
0.2435
0.2227
−32%


Metabolite - 4500
50
0.2437
0.2227
−62%


Metabolite - 3667
35
0.2468
0.2245
−20%


Metabolite - 4495
50
0.2517
0.228
−22%


Metabolite - 3706
35
0.2536
0.2286
−17%


D-lyxose
50
0.2626
0.2336
−26%


glutamine
50
0.2629
0.2336
−28%


Metabolite - 3014
50
0.2637
0.2336
−21%


Metabolite - 3802
35
0.2638
0.2336
−34%


Metabolite - 2591
35
0.2717
0.2375
32%


Metabolite - 3178-possible-NH3-adduct-
35
0.2724
0.2375
−28%


of-isobar-42


Metabolite - 2607
35
0.2727
0.2375
−38%


L-kynurenine
35
0.2729
0.2375
−76%


gamma-L-glutamyl-L-tyrosine
35
0.2752
0.2385
−23%


Metabolite - 3832-possible-phenol-
35
0.2771
0.2391
66%


sulfate


hippuric acid
35
0.2825
0.2427
−21%


4-hydroxyphenylacetate
35; 50
0.2898
0.2469
−24%


Metabolite - 3108
50
0.2898
0.2469
−34%


Metabolite - 3834
35
0.2916
0.2473
−33%


allantoin
35
0.2933
0.2478
−19%


Metabolite - 2118
35
0.2957
0.2488
−19%


Metabolite - 3440
35
0.2986
0.2501
192%


ascorbic acid
50
0.3011
0.2502
−70%


Metabolite - 1498
35
0.3011
0.2502
−40%


Metabolite - 4509
50
0.3032
0.2508
−38%


Isobar-6-includes-valine-betaine
35
0.3058
0.2519
−16%


Metabolite - 2150
35
0.312
0.2556
−24%


Metabolite - 3911
35
0.3148
0.2556
−14%


1-5-diaminopentane
50
0.3158
0.2556
−40%


proline
35; 50
0.3161
0.2556
−29%


salicyluric acid
35
0.3167
0.2556
−71%


Metabolite - 4494
50
0.3178
0.2556
14%


porphobilinogen
35
0.3208
0.2569
−20%


Metabolite - 3804
35
0.3263
0.2589
−21%


pantothenic acid
35
0.3273
0.2589
−36%


Metabolite - 3099
50
0.3281
0.2589
−25%


Metabolite - 3660
35
0.3284
0.2589
−39%


Metabolite - 3090
50
0.3345
0.2598
−11%


Metabolite - 4632
50
0.3356
0.2598
−45%


Isobar-2-includes-3-amino-isobutyrate-
35
0.3373
0.2598
183%


2-amino-butyrate-4-aminobutanoic acid-


dimethylglycine-choline-


Metabolite - 3309
35
0.3374
0.2598
−18%


Metabolite - 1110
35
0.3379
0.2598
−17%


Metabolite - 3493
35
0.3384
0.2598
−17%


Metabolite - 3163-possible-
35
0.3387
0.2598
−15%


methylcytidine-benserazide-or-Pyr-Gln-


OH


N-alpha-acetyl-L-ornithine-
50
0.345
0.2637
−16%


Metabolite - 1465
35
0.3552
0.2705
−14%


Metabolite - 1834
35
0.3614
0.2729
53%


3-methyl-L-histidine
35
0.3622
0.2729
−14%


carnitine
35
0.3625
0.2729
32%


Metabolite - 1338
35
0.3638
0.2729
25%


dulcitol
50
0.3732
0.2789
−36%


glutamic acid
50
0.3771
0.2808
−15%


Metabolite - 2259
35
0.3795
0.2815
−42%


S-adenosyl-l-homocysteine
35
0.3841
0.2839
−19%


D-allose
50
0.3895
0.2858
−21%


Metabolite - 4234
35
0.3895
0.2858
−51%


Metabolite - 3091
50
0.3975
0.2906
−27%


2-deoxy-D-glucose
50
0.4016
0.292
−26%


Metabolite - 3963
35
0.4038
0.292
−54%


Metabolite - 2292
35
0.4038
0.292
23%


isoleucine
50
0.4077
0.2936
−15%


Metabolite - 2893-possible-
35
0.4115
0.2936
−21%


demethylated-Rosiglitazone


glucose-6-phosphate
50
0.4136
0.2936
189%


2-keto-L-gulonic acid
50
0.4138
0.2936
194%


Metabolite - 1496
35
0.4148
0.2936
−31%


theobromine-theophylline
35
0.418
0.2944
41%


Metabolite - 3131
35
0.42
0.2944
−19%


Metabolite - 3085
50
0.4202
0.2944
38%


Metabolite - 3893
35
0.4258
0.2971
−15%


Metabolite - 2686
35
0.4273
0.2971
−15%


Metabolite - 2386
35
0.4286
0.2971
−13%


Metabolite - 2108
35
0.432
0.2981
55%


Metabolite - 2249
35
0.4331
0.2981
−30%


Metabolite - 3604
35
0.4379
0.3004
−16%


Metabolite - 3543
35
0.4474
0.3041
−42%


Metabolite - 3878
35
0.4474
0.3041
25%


Metabolite - 4507
50
0.4492
0.3041
−21%


Metabolite - 3771
35
0.4493
0.3041
−28%


3-nitro-L-tyrosine
50; 35
0.4548
0.3062
−20%


lactate
50
0.4554
0.3062
14%


Metabolite - 3668
35
0.4624
0.3084
12%


Metabolite - 2506
35
0.4645
0.3084
−18%


Metabolite - 2254
35
0.4659
0.3084
69%


Isobar-13-includes-5-keto-D-gluconic
35
0.4661
0.3084
−34%


acid-2-keto-L-gulonic acid-D-glucuronic


acid


Metabolite - 3909
35
0.4663
0.3084
55%


Metabolite - 1682
35
0.4794
0.3142
−16%


dethiobiotin
50; 35
0.4799
0.3142
−39%


alpha-L-sorbopyranose
50
0.482
0.3142
−29%


beta-D-lactose
50
0.4838
0.3142
−21%


Metabolite - 2329
35
0.4846
0.3142
−11%


Metabolite - 4520
50
0.4866
0.3145
32%


Metabolite - 1114
35
0.4884
0.3147
−21%


malic acid
35
0.49
0.3147
−15%


Metabolite - 4501
50
0.4979
0.3188
−19%


Metabolite - 3436
35
0.5088
0.3247
−11%


Metabolite - 1351
35
0.5117
0.3255
−21%


Metabolite - 3806
35
0.5173
0.3281
−24%


Metabolite - 2726
35
0.519
0.3281
−12%


Metabolite - 4518
50
0.5282
0.3329
−32%


Metabolite - 3409
35
0.5303
0.3331
−17%


Metabolite - 4133
50
0.5446
0.341
−21%


Metabolite - 3952
35
0.547
0.3415
−20%


Metabolite - 3879
35
0.5531
0.3442
−27%


Metabolite - 3113
50
0.5631
0.3488
17%


Metabolite - 3433
35
0.5639
0.3488
−9%


tartaric acid
35
0.5703
0.3517
−20%


Metabolite - 2698
35
0.5772
0.3549
38%


Metabolite - 2056
35
0.5849
0.3582
−8%


Metabolite - 3670
35
0.5873
0.3582
−9%


Metabolite - 3786
35
0.5899
0.3582
−14%


Metabolite - 2853
35
0.5908
0.3582
−16%


Metabolite - 3981
35
0.5931
0.3582
−21%


Metabolite - 3564
35
0.5948
0.3582
−23%


Metabolite - 3781-possible-Na-adduct-
35
0.5951
0.3582
−12%


of-Isobar-21


Metabolite - 1186
35
0.5992
0.3585
−11%


2-isopropylmalic acid
50
0.5992
0.3585
37%


Isobar-1-includes-mannose-fructose-
35
0.6073
0.3623
26%


glucose-galactose-alpha-L-


sorbopyranose-Inositol-D-allose


Metabolite - 1101
35
0.6174
0.3672
−10%


Metabolite - 4167
35
0.6297
0.3734
−10%


Metabolite - 2005
35
0.6452
0.3814
−9%


sn-Glycerol-3-phosphate
50
0.65
0.3814
−13%


3-methylglutaric acid
35
0.6501
0.3814
9%


Metabolite - 3992-possible-Cl-adduct-
35
0.6507
0.3814
−5%


of-Formate-dimer


mercaptopyruvate
35
0.6565
0.383
−12%


homogentisate
35
0.6586
0.383
−9%


azelaic acid
35
0.6592
0.383
18%


Metabolite - 4510
50
0.6672
0.3866
−13%


3-hydroxyphenylacetate
35
0.674
0.3883
−10%


Metabolite - 3127
35
0.6771
0.3883
−9%


phosphoenolpyruvate
35
0.6772
0.3883
−17%


Metabolite - 3138
35
0.6779
0.3883
−10%


agmatine
35
0.6825
0.3898
−15%


Metabolite - 3402
35
0.6861
0.3899
−6%


alpha-keto-glutarate
35
0.7074
0.4
−11%


Metabolite - 4512
50
0.7083
0.4
−17%


Metabolite - 2323
35
0.7136
0.4012
−9%


Metabolite - 3701
35
0.7145
0.4012
−10%


Metabolite - 3016
50
0.73
0.4068
4%


Metabolite - 2272
35
0.7302
0.4068
−17%


DL-pipecolic acid
35
0.7319
0.4068
−12%


Metabolite - 4633
50
0.7325
0.4068
−8%


niacinamide
35
0.7378
0.4086
8%


Metabolite - 3123
35
0.7434
0.41
−8%


galactose
50
0.7512
0.41
−13%


pyridoxamine-phosphate
35
0.752
0.41
5%


Metabolite - 3101
50
0.7539
0.41
−7%


o-phosphoethanolamine
50
0.756
0.41
−8%


Metabolite - 3516
35
0.7584
0.41
−7%


DL-indole-3-lactic acid
50; 35
0.76
0.41
11%


Metabolite - 1126
35
0.7615
0.41
−9%


Metabolite - 1981
35
0.7617
0.41
−6%


Metabolite - 3986
35
0.7628
0.41
−8%


Metabolite - 4598
50
0.7687
0.4121
−7%


Metabolite - 4514
50
0.775
0.4127
9%


Metabolite - 3507
35
0.7759
0.4127
−7%


Metabolite - 1216
35
0.776
0.4127
4%


Metabolite - 3053
35
0.788
0.4172
−12%


L-rhamnose
50
0.7886
0.4172
5%


Metabolite - 2389
35
0.7912
0.4175
6%


Metabolite - 1368
35
0.7964
0.4191
−11%


alphahydroxybenzeneacetic acid
35
0.7995
0.4196
−4%


benzoic acid
50; 35
0.809
0.4235
6%


N-acetyl-L-alanine
35
0.8203
0.4259
−4%


Metabolite - 4517
50
0.8203
0.4259
−6%


Metabolite - 4092
35
0.8218
0.4259
−6%


Metabolite - 3977
35
0.8221
0.4259
−8%


Isobar-38-includes-N-acetyl-L-
35
0.8281
0.428
4%


methionine-5-hydroxy-1H-indole-3-


acetic acid


Metabolite - 2706
35
0.8316
0.4284
6%


Metabolite - 3311-possible-Zolpidem-in-
35
0.8367
0.4284
7%


humans-


Metabolite - 4010
50
0.8374
0.4284
−6%


Metabolite - 3773
35
0.8375
0.4284
−5%


Metabolite - 2897
35
0.847
0.4322
5%


Metabolite - 3364
35
0.8537
0.434
5%


Metabolite - 3231
35
0.8549
0.434
−4%


Metabolite - 3957
35
0.8591
0.435
−3%


Metabolite - 2269-
35
0.8619
0.4353
−3%


Metabolite - 3754
35
0.873
0.4398
5%


Metabolite - 2387
35
0.8782
0.4414
−5%


Metabolite - 3377
35
0.8819
0.4421
−6%


Metabolite - 2319
35
0.8913
0.445
−3%


suberic acid
35
0.8921
0.445
3%


oxalacetic acid
35
0.8946
0.4451
−2%


Metabolite - 3876
35
0.8969
0.4451
−6%


Metabolite - 2348
35
0.8988
0.4451
−4%


Metabolite - 1839
35
0.9015
0.4453
5%


Metabolite - 1113-possible-
35
0.9057
0.4462
−4%


acetylcarnitine-or-isopentyl-adenine


3-methyl-2-oxovaleric acid
35
0.9096
0.4469
−4%


melibiose
50
0.9114
0.4469
4%


Metabolite - 1364
35
0.9316
0.4557
3%


Metabolite - 4524
50
0.9364
0.4569
4%


thymidine
35
0.9412
0.4581
2%


Metabolite - 3755
35
0.9473
0.46
−1%


Metabolite - 3855
35
0.9504
0.4604
−1%


Metabolite - 3058
50
0.966
0.4638
2%


Metabolite - 1116
35
0.9663
0.4638
−1%


Metabolite - 3847
35
0.9693
0.4638
−1%


Metabolite - 3313
35
0.9709
0.4638
−1%


5-s-methyl-5-thioadenosine
35
0.9714
0.4638
1%


Metabolite - 3887
35
0.9799
0.4668
−1%


Metabolite - 3824
35
0.9839
0.4676
0%


Metabolite - 3457
35
0.9863
0.4676
−1%


Metabolite - 1283
35
0.9995
0.4728
0%









Example 3
Distinguish Lower Grade from Higher Grade/Metastatic Prostate Cancer in Subjects Using Plasma
Biomarkers were discovered by (1) analyzing plasma samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
The plasma samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer, 43 individuals with lower grade prostate cancer (i.e. Gleason Score major=3) and 15 individuals with aggressive, higher grade prostate cancer (i.e. Gleason Score major=4+). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Control, Metastatic/Higher Grade Prostate cancer vs. Lower Grade Prostate cancer).
Biomarkers:
As listed below in Table 6, biomarkers were discovered that were differentially present between plasma samples from subjects with lower grade prostate cancer and plasma samples from Control subjects with negative prostate biopsies (i.e. not diagnosed with prostate cancer). Table 7 lists biomarkers that were discovered that were differentially present between plasma samples from subjects with metastatic/high grade prostate cancer and plasma samples from Control subjects with biopsy negative prostates (i.e. not diagnosed with prostate cancer). Table 8 lists biomarkers that were discovered that were differentially present between plasma samples from subjects with metastatic/high grade prostate cancer and plasma from subjects with lower grade prostate cancer.
Tables 6-8 include, for each listed biomarker, the p-value and the q-value determined in the statistical analysis of the data concerning the biomarkers and an indication of the percentage difference in the lower grade prostate cancer mean level as compared to the control mean level (Table 6), the metastatic/high grade prostate cancer mean level as compared to the control mean level (Table 7), and the metastatic/high grade prostate cancer mean level as compared to the lower grade prostate cancer mean level (Table 8). The term “Isobar” as used in the tables indicates the compounds that could not be distinguished from each other on the analytical platform used in the analysis (i.e., the compounds in an isobar elute at nearly the same time and have similar (and sometimes exactly the same) quant ions, and thus cannot be distinguished). Library indicates the chemical library that was used to identify the compounds. The number 50 refers to the GC library and the number 35 refers to the LC library.
Biomarkers were discovered by (1) analyzing plasma samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
The plasma samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer, 43 individuals with lower grade prostate cancer (i.e. Gleason Score major=3) and 15 individuals with aggressive, high grade prostate cancer (i.e. Gleason Score major=4+). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Lower Grade Prostate cancer).







TABLE 6







Plasma Metabolite Biomarkers to distinguish Non-cancer vs. Lower Grade PCA

















%







Change


COMP_ID
COMPOUND
LIB_ID
pvalue
qvalue
in PCA















53
glutamine
50
0.9855
0.9993
−1% 


54
tryptophan
50
0.6455
0.9851
3%


57
glutamic acid
50
0.5953
0.9851
−6% 


59
histidine
50
0.4258
0.9478
−9% 


60
leucine
50
0.2512
0.9478
8%


63
cholesterol
50
0.8251
0.9851
−1% 


64
phenylalanine
35
0.61
0.9851
−2% 


513
creatinine
35
0.0047
0.5749
−10% 


527
lactate
50
0.6496
0.9851
−1% 


528
alpha - keto-glutarate
35
0.0081
0.5749
−40% 


541
4-hydroxyphenylacetate
35
0.2553
0.9478
−5% 


542
3-hydroxybutanoic acid
50
0.748
0.9851
11% 


569
caffeine
35
0.0542
0.7407
61% 


577
fructose
50
0.2415
0.9478
−26% 


581
glucose
50
0.254
0.9478
−4% 


584
mannose
50
0.9209
0.9993
1%


594
niacinamide
35
0.7471
0.9851
10% 


597
phosphoenolpyruvate
35
0.5253
0.9851
−6% 


1105
linoleic acid
50
0.6374
0.9851
3%


1107
allantoin
50
0.6861
0.9851
−8% 


1110
arachidonic acid
50
0.4338
0.9478
−6% 


1121
heptadecanoic acid
50
0.0432
0.7407
12% 


1123
inosine
35
0.8138
0.9851
8%


1125
isoleucine
50
0.2856
0.9478
7%


1126
alanine
50
0.8973
0.9993
−1% 


1284
threonine
50
0.9044
0.9993
−1% 


1299
tyrosine
50
0.2074
0.9478
8%


1302
methionine
35
0.9843
0.9993
0%


1303
malic acid
35
0.5347
0.9851
−9% 


1336
n-hexadecanoic acid
50
0.4029
0.9478
5%


1358
octadecanoic acid
50
0.05
0.7407
7%


1365
tetradecanoic acid
50
0.4504
0.9478
6%


1366
trans-4-hydroxyproline
50
0.8095
0.9851
1%


1413
3-hydroxyphenylacetate
35
0.4804
0.9659
−3% 


1414
3-phospho-d-glycerate
35
0.9448
0.9993
−1% 


1415
4-amino-5-methyl-2-1H-
35
0.6722
0.9851
3%



pyrimidinone


1431
(p-Hydroxyphenyl)lactic acid
50
0.598
0.9851
6%


1432
alphahydroxybenzeneacetic
35
0.8582
0.9851
−2% 



acid


1437
succinate
50
0.6649
0.9851
−2% 


1444
DL-pipecolic acid
35
0.3051
0.9478
−10% 


1480
guanidineacetic acid
35
0.3889
0.9478
7%


1493
ornithine
50
0.9114
0.9993
1%


1494
5-oxoproline
50
0.5882
0.9851
4%


1498
N-6-trimethyl-1-lysine
35
0.2178
0.9478
−11% 


1507
palmitoleic acid
50
0.5998
0.9851
8%


1508
pantothenic acid
35
0.4151
0.9478
20% 


1519
sucrose
50
0.6854
0.9851
6%


1557
3-methylglutaric acid
35
0.1656
0.9478
−9% 


1561
alpha - tocopherol
50
0.0145
0.6753
−50% 


1564
citric acid
50
0.6977
0.9851
2%


1570
oleic acid
50
0.8649
0.9851
−2% 


1572
glyceric acid
50
0.7217
0.9851
2%


1574
histamine
35
0.5568
0.9851
8%


1584
methyl-indole-3-acetate
35
0.9677
0.9993
0%


1587
N-acetyl-L-leucine
35
0.3101
0.9478
31% 


1591
N-acetyl-L-valine
35
0.0094
0.5749
20% 


1604
uric acid
35
0.9975
0.9993
0%


1643
fumaric acid
50
0.5347
0.9851
−3% 


1645
n-dodecanoate
50
0.7836
0.9851
3%


1648
serine
50
0.2503
0.9478
8%


1649
valine
50
0.3429
0.9478
7%


1670
urea
50
0.5816
0.9851
4%


1708
7-8-dihydrofolic acid
35
0.3763
0.9478
30% 


1898
proline
50
0.6963
0.9851
−3% 


2078
pyrophosphate
35
0.97
0.9993
0%


2092
catechol
35
0.9928
0.9993
0%


2132
citrulline
50
0.7476
0.9851
−3% 


2730
gamma - L-glutamyl-L-
35
0.8715
0.9852
−3% 



glutamine


2734
gamma - L-glutamyl-L-
35
0.2947
0.9478
6%



tyrosine


2832
adenosine-5-monophosphate
35
0.661
0.9851
−4% 


2848
guanosine-5-diphosphate
35
0.9286
0.9993
1%


3127
hypoxanthine
35
0.6226
0.9851
−6% 


3138
pyridoxamine-phosphate
35
0.1559
0.9478
16% 


3147
xanthine
35
0.4283
0.9478
−10% 


4966
xylitol
35
0.6274
0.9851
5%


5280
biliverdin
35
0.2685
0.9478
33% 


5331
pyridoxal-phosphate
35
0.2348
0.9478
−5% 


5618
Metabolite - 1085-possible-
35
0.4282
0.9478
4%



isolobinine-or-4-aminoestra -



1-3-5-10-triene-3-17beta - diol


5628
Metabolite - 1086
35
0.8863
0.9931
−2% 


5669
Metabolite - 1104
35
0.7565
0.9851
−1% 


5687
Metabolite - 1110
35
0.8421
0.9851
5%


5689
Metabolite - 1111-possible-
35
0.1327
0.9478
11% 



methylnitronitrosoguanidine-



or-ethyl-thiocarbamoylacetate


5697
acetylcarnitine-
35
0.8273
0.9851
−2% 


5717
Metabolite - 1121
35
0.2772
0.9478
10% 


5733
Metabolite - 1127
35
0.0093
0.5749
−18% 


5765
Metabolite - 1142-possible-5-
35
0.7839
0.9851
9%



hydroxypentanoate-or-beta -



hydroxyisovaleric acid


5788
Metabolite - 1183
35
0.3488
0.9478
145% 


5792
Metabolite - 1185
35
0.001
0.3826
35% 


5800
Metabolite - 1188
35
0.0412
0.7407
36% 


6112
Metabolite - 1203-HXGXX -
35
0.3191
0.9478
53% 



in-MTRX


6130
Metabolite - 1208
35
0.7504
0.9851
7%


6136
Metabolite - 1211-possible-
35
0.0416
0.7407
287% 



IHWESASLLR-


6144
Metabolite - 1215
35
0.9559
0.9993
2%


6147
Metabolite - 1216
35
0.6032
0.9851
8%


6155
Metabolite - 1220
35
0.8003
0.9851
3%


6171
Metabolite - 1244
35
0.3509
0.9478
11% 


6266
Metabolite - 1286
35
0.3935
0.9478
5%


6278
Metabolite - 1289
35
0.1436
0.9478
−16% 


6362
Metabolite - 1323-possible-p-
35
0.3987
0.9478
17% 



cresol-sulfate


6398
Metabolite - 1335
35
0.9275
0.9993
−1% 


6413
Metabolite - 1342-possible-
35
0.3835
0.9478
16% 



phenylacetylglutamine-or-



formyl-N-acetyl-5-



methoxykynurenamine


6437
Metabolite - 1349-possible-N-
35
0.9654
0.9993
1%



acetyl-8-O-methyl-Neuraminic



acid


6443
Metabolite - 1351
35
0.9312
0.9993
−1% 


6537
Metabolite - 1389-possible-
35
0.3189
0.9478
308% 



gemfibrozil-glucuronide-


6549
Metabolite - 1392
35
0.4102
0.9478
12% 


6787
Metabolite - 1465
35
0.7835
0.9851
5%


6852
Metabolite - 1498
35
0.1492
0.9478
−14% 


6987
Metabolite - 1573
35
0.8168
0.9851
−2% 


7029
Metabolite - 1597
35
0.0206
0.7407
10% 


7081
Metabolite - 1609
35
0.3186
0.9478
8%


7177
Metabolite - 1656
35
0.8442
0.9851
2%


7359
n-acetyl-L-aspartic acid
35
0.7069
0.9851
−2% 


7446
p-hydroxybenzaldehyde
35
0.3568
0.9478
−6% 


7595
Metabolite - 1817
35
0.6472
0.9851
3%


7639
oxalic acid
35
0.7835
0.9851
2%


7644
Metabolite - 1831-possible-Cl-
35
0.2483
0.9478
−29% 



adduct-of-citrulline


7650
Metabolite - 1834
35
0.6754
0.9851
−8% 


7652
Metabolite - 1835
35
0.031
0.7407
25% 


7654
Metabolite - 1836
35
0.7242
0.9851
−3% 


7660
Metabolite - 1839
35
0.8404
0.9851
−4% 


7672
Metabolite - 1843
35
0.7507
0.9851
3%


7933
Metabolite - 1911
35
0.0739
0.7639
48% 


7935
paraxanthine
35
0.1117
0.9478
38% 


7941
Metabolite - 1914
35
0.8081
0.9851
6%


7944
Metabolite - 1915
35
0.3455
0.9478
55% 


7957
trans-2-3-4-
35
0.8125
0.9851
5%



trimethoxycinnamic acid


8091
glycocholic acid
35
0.2546
0.9478
30% 


8176
Metabolite - 1974
35
0.4143
0.9478
10% 


8189
Metabolite - 1977
35
0.8558
0.9851
2%


8196
Metabolite - 1979-Cl-adduct-
35
0.5336
0.9851
−5% 



of-isobar-19


8217
Metabolite - 1983
35
0.1187
0.9478
410% 


8300
Metabolite - 1988
35
0.1698
0.9478
−14% 


8336
Metabolite - 2005
35
0.8806
0.9897
−2% 


8404
Metabolite - 2027
35
0.6346
0.9851
−4% 


8649
Metabolite - 2053
35
0.2084
0.9478
17% 


8669
Metabolite - 2055
35
0.9233
0.9993
1%


8677
Metabolite - 2056
35
0.5835
0.9851
6%


8796
Metabolite - 2074
35
0.8013
0.9851
−2% 


8959
Metabolite - 2100
35
0.4481
0.9478
5%


9007
Metabolite - 2108
35
0.9789
0.9993
0%


9024
Metabolite - 2111
35
0.6202
0.9851
−5% 


9092
Metabolite - 2129
35
0.5701
0.9851
−9% 


9106
Metabolite - 2130
35
0.4394
0.9478
−12% 


9130
Metabolite - 2139
35
0.7305
0.9851
3%


9137
Metabolite - 2141
35
0.5077
0.9851
12% 


9491
Metabolite - 2185
35
0.0387
0.7407
18% 


9748
Metabolite - 2212
35
0.3479
0.9478
−9% 


10087
Metabolite - 2249
35
0.6712
0.9851
−4% 


10092
Metabolite - 2250
35
0.0564
0.7407
63% 


10122
Metabolite - 2254
35
0.4991
0.9851
−15% 


10143
Metabolite - 2255-
35
0.0474
0.7407
89% 



hydroxyproline-form-of-



bradykinin


10145
Metabolite - 2256
35
0.1134
0.9478
−18% 


10245
Metabolite - 2269-
35
0.7452
0.9851
8%


10317
Metabolite - 2279
35
0.2635
0.9478
32% 


10327
Metabolite - 2281
35
0.5771
0.9851
34% 


10378
Metabolite - 2287
35
0.395
0.9478
59% 


10438
gamma - glu-leu
35
0.4307
0.9478
4%


10461
Metabolite - 2313
35
0.71
0.9851
−4% 


10476
Metabolite - 2316
35
0.456
0.9478
−13% 


10544
Metabolite - 2329
35
0.8979
0.9993
1%


10551
Metabolite - 2347
35
0.6776
0.9851
8%


10604
Metabolite - 2370
35
0.6853
0.9851
4%


10629
Metabolite - 2386
35
0.8269
0.9851
−4% 


10644
Metabolite - 2387
35
0.5459
0.9851
52% 


10655
Metabolite - 2388
35
0.7697
0.9851
−1% 


10667
Metabolite - 2389
35
0.318
0.9478
20% 


10672
Metabolite - 2390
35
0.4169
0.9478
23% 


10692
Metabolite - 2391
35
0.397
0.9478
−6% 


10698
Metabolite - 2392
35
0.7279
0.9851
−9% 


10737
Isobar-1-includes-mannose-
35
0.7112
0.9851
4%



fructose-glucose-galactose-



alpha - L-sorbopyranose-



Inositol-D-allose-D--altrose-D-



psicone


10739
Metabolite - 2407
35
0.9869
0.9993
0%


10741
Isobar-2-includes-2-
35
0.6711
0.9851
−10% 



aminoisobutyric acid-3-amino-



isobutyrate-2-amino-butyrate-



4-aminobutanoic acid-



dimethylglycine-choline-


10743
Isobar-4-includes-Gluconic
35
0.8686
0.9851
−2% 



acid-DL-arabinose-D-ribose-L-



xylose-DL-lyxose-D-xylulose


10744
Isobar-5-includes-asparagine-
35
0.7225
0.9851
4%



ornithine-gly-gly


10746
Isobar-6-includes-valine-
35
0.1667
0.9478
5%



betaine


10753
Isobar-9-includes-galactinol-
35
0.6051
0.9851
−7% 



dihydrate-turanose-kojibiose-



D-leucrose-lactulose-



sophorose-sucrose-beta - D-



lactose-D-trehalose-D-



cellobiose-D-Maltose-



palatinose-melibiose-alpha -



D-lactose


10782
Metabolite - 2486
35
0.5968
0.9851
8%


10785
Metabolite - 2506
35
0.9224
0.9993
2%


10787
Metabolite - 2507
35
0.6105
0.9851
−13% 


10825
Metabolite - 2546
35
0.9993
0.9993
0%


11053
Metabolite - 2567
35
0.1285
0.9478
9%


11111
Metabolite - 2592
35
0.4637
0.9582
54% 


11219
Metabolite - 2686
35
0.5844
0.9851
3%


11222
Metabolite - 2688
35
0.163
0.9478
14% 


11323
Metabolite - 2711
35
0.9889
0.9993
0%


11438
phosphate
50
0.8104
0.9851
0%


11499
Metabolite - 2753
35
0.4215
0.9478
7%


11777
glycine
50
0.3338
0.9478
−8% 


11813
Metabolite - 2809
35
0.8323
0.9851
3%


12035
nonanate
50
0.7544
0.9851
1%


12109
Metabolite - 2853
35
0.0277
0.7407
39% 


12298
Metabolite - 2867
35
0.1237
0.9478
−45% 


12478
Metabolite - 2898
35
0.0495
0.7407
−51% 


12532
Metabolite - 2914
50
0.1166
0.9478
2%


12533
Metabolite - 2915
50
0.2615
0.9478
−7% 


12543
2-hydroxy-butanoic acid
50
0.1956
0.9478
17% 


12562
Metabolite - 2955
50
0.279
0.9478
3%


12593
Metabolite - 2973
50
0.9818
0.9993
0%


12594
Metabolite - 2974
50
0.9799
0.9993
0%


12601
Metabolite - 2978
50
0.6254
0.9851
3%


12625
Metabolite - 3002
50
0.9162
0.9993
−2% 


12626
Metabolite - 3003
50
0.1382
0.9478
−9% 


12627
Metabolite - 3004
50
0.5311
0.9851
−5% 


12639
Metabolite - 3012
50
0.4723
0.9653
5%


12641
meso-erythritol
50
0.3847
0.9478
−7% 


12644
Metabolite - 3016
50
0.1293
0.9478
−7% 


12645
Metabolite - 3017
50
0.0303
0.7407
18% 


12647
Metabolite - 3019
50
0.2488
0.9478
7%


12648
Metabolite - 3020
50
0.4953
0.9851
6%


12650
Metabolite - 3022
50
0.9679
0.9993
0%


12656
Metabolite - 3025
50
0.195
0.9478
8%


12658
Metabolite - 3026
50
0.3559
0.9478
7%


12663
Metabolite - 3030
50
0.0934
0.9247
9%


12666
Metabolite - 3033
50
0.8631
0.9851
−1% 


12673
Metabolite - 3040
50
0.3373
0.9478
10% 


12682
Metabolite - 3044
35
0.1918
0.9478
12% 


12719
Metabolite - 3055
35
0.741
0.9851
5%


12720
Metabolite - 3056
35
0.5288
0.9851
−4% 


12726
Metabolite - 3058
50
0.727
0.9851
3%


12739
1-5-anhydro-D-glucitol
50
0.2751
0.9478
−8% 


12751
Metabolite - 3073
50
0.921
0.9993
1%


12753
Metabolite - 3074
50
0.3835
0.9478
−22% 


12754
Metabolite - 3075
50
0.2497
0.9478
−7% 


12756
Metabolite - 3077
50
0.9463
0.9993
1%


12757
Metabolite - 3078
50
0.8351
0.9851
−2% 


12761
Metabolite - 3081
50
0.0685
0.7493
−9% 


12765
inositol
50
0.4516
0.9478
−5% 


12768
Metabolite - 3088
50
0.1228
0.9478
−15% 


12769
Metabolite - 3089
50
0.0654
0.7493
16% 


12771
Metabolite - 3091
50
0.25
0.9478
21% 


12773
Metabolite - 3093
50
0.4676
0.961
9%


12774
Metabolite - 3094
50
0.9437
0.9993
0%


12777
Metabolite - 3097
50
0.2879
0.9478
16% 


12780
Metabolite - 3098
50
0.1558
0.9478
12% 


12781
Metabolite - 3099
50
0.0718
0.7631
26% 


12784
Metabolite - 3102
50
0.8378
0.9851
−1% 


12790
Metabolite - 3108
50
0.6368
0.9851
2%


12876
Metabolite - 3125
35
0.4896
0.9793
−4% 


12912
Metabolite - 3129
35
0.4506
0.9478
9%


12924
Metabolite - 3131
35
0.6823
0.9851
5%


12931
DL-hexanoyl-carnitine
35
0.6978
0.9851
3%


12960
Metabolite - 3134
35
0.9924
0.9993
0%


12969
Metabolite - 3135
35
0.5304
0.9851
13% 


13018
Metabolite - 3138
35
0.0971
0.9247
−16% 


13038
Metabolite - 3143
35
0.9259
0.9993
1%


13065
Metabolite - 3146
35
0.8545
0.9851
4%


13104
Metabolite - 3160
35
0.2622
0.9478
−10% 


13142
Metabolite - 3165
35
0.3363
0.9478
−5% 


13146
Metabolite - 3166
35
0.8043
0.9851
4%


13148
Metabolite - 3167
35
0.044
0.7407
21% 


13179
possible-Metabolite - 3176-
35
0.7152
0.9851
5%



possible-creatine


13208
Metabolite - 3181
35
0.354
0.9478
−9% 


13211
Metabolite - 3182
35
0.9963
0.9993
0%


13214
Metabolite - 3183-possible-
35
0.7525
0.9851
2%



gamma - L-glutamyl-L-



phenylalanine


13217
Metabolite - 3184
35
0.1642
0.9478
−11% 


13249
Metabolite - 3215
35
0.6878
0.9851
−4% 


13251
Metabolite - 3216
35
0.2268
0.9478
−13% 


13257
Metabolite - 3218
35
0.5081
0.9851
5%


13342
Metabolite - 3243
35
0.5847
0.9851
10% 


13448
Metabolite - 3303
35
0.0978
0.9247
−9% 


13459
Metabolite - 3305
35
0.3143
0.9478
−19% 


13484
Metabolite - 3309
35
0.0626
0.7493
−25% 


13505
Metabolite - 3313
35
0.5629
0.9851
−23% 


13509
Metabolite - 3314
35
0.2956
0.9478
−8% 


13534
Metabolite - 3320-possible-
35
0.7791
0.9851
10% 



pimpinellin-or-



tetrahydroxybenzophenone


13545
Metabolite - 3322
35
0.2266
0.9478
16% 


13589
Metabolite - 3327
35
0.831
0.9851
−4% 


13775
Metabolite - 3370
35
0.8025
0.9851
1%


13803
Metabolite - 3377
35
0.2963
0.9478
−17% 


13904
Metabolite - 3402
35
0.3454
0.9478
−15% 


14027
Metabolite - 3426
35
0.1435
0.9478
−3% 


14084
Metabolite - 3436
35
0.2313
0.9478
13% 


14117
Metabolite - 3441
35
0.2102
0.9478
−10% 


14239
Metabolite - 3474
35
0.3092
0.9478
−9% 


14249
Metabolite - 3476
35
0.3874
0.9478
−16% 


14368
Metabolite - 3489
35
0.383
0.9478
−19% 


14439
Metabolite - 3498
35
0.7901
0.9851
3%


14495
Metabolite - 3534
35
0.2653
0.9478
13% 


14595
Metabolite - 3576
35
0.6382
0.9851
−5% 


14608
Metabolite - 3578
35
0.243
0.9478
13% 


14639
Metabolite - 3603
35
0.04
0.7407
19% 


14640
Metabolite - 3604
35
0.2069
0.9478
30% 


14672
Metabolite - 3615
35
0.275
0.9478
15% 


14715
Metabolite - 3653-possible-
35
0.6884
0.9851
−12% 



stachydrine-


14766
Metabolite - 3670
35
0.1501
0.9478
8%


14785
isobar-glycochenodeoxycholic
35
0.3915
0.9478
18% 



acid-glycodeoxycholic acid


14787
Metabolite - 3698
35
0.3714
0.9478
−11% 


14837
Metabolite - 3707
35
0.4795
0.9659
18% 


14961
Metabolite - 3752
35
0.0597
0.7407
228% 


15000
Metabolite - 3758
35
0.3269
0.9478
−23% 


15017
Metabolite - 3761
35
0.6023
0.9851
−5% 


15032
Metabolite - 3765
35
0.0289
0.7407
43% 


15063
Metabolite - 3772
35
0.573
0.9851
−4% 


15113
Metabolite - 3783
35
0.983
0.9993
0%


15122
glycerol
50
0.7135
0.9851
−2% 


15128
DL-homocysteine
35
0.1339
0.9478
−14% 


15129
D-alanyl-D-alanine
35
0.0165
0.6833
23% 


15211
Metabolite - 3807
35
0.3174
0.9478
−5% 


15220
Metabolite - 3813
35
0.6421
0.9851
−5% 


15227
Metabolite - 3816
35
0.9802
0.9993
0%


15251
Metabolite - 3830
35
0.262
0.9478
20% 


15253
Metabolite - 3832-possible-
35
0.0596
0.7407
−45% 



phenol-sulfate


15278
Metabolite - 3843
35
0.0092
0.5749
−16% 


15319
DL-phenyllactic acid
35
0.2331
0.9478
32% 


15326
Metabolite - 3879
35
0.5692
0.9851
13% 


15328
azelaic acid
35
0.7398
0.9851
−2% 


15336
tartaric acid
35
0.9993
0.9993
0%


15365
sn-Glycerol-3-phosphate
50
0.4116
0.9478
3%


15389
Metabolite - 3900
35
0.5829
0.9851
3%


15500
carnitine
35
0.528
0.9851
3%


15529
Metabolite - 3951
35
0.0399
0.7407
−11% 


15535
Metabolite - 3955
35
0.5955
0.9851
−7% 


15606
Metabolite - 3968
35
0.761
0.9851
−5% 


15612
Metabolite - 3972
35
0.2908
0.9478
8%


15626
Metabolite - 3977
35
0.2184
0.9478
−7% 


15677
3-methyl-L-histidine
35
0.1203
0.9478
−8% 


15681
4-Guanidinobutanoic acid
35
0.2211
0.9478
−14% 


15683
4-methyl-2-oxopentanoate
50
0.4541
0.9478
5%


15704
heptanedioic acid
35
0.8664
0.9851
−2% 


15744
N-N-dimethylarginine
35
0.6586
0.9851
3%


15753
hippuric acid
35
0.6181
0.9851
10% 


15991
L-alpha -
35
0.8467
0.9851
−3% 



glycerophosphorylcholine


16002
Metabolite - 3992-possible-Cl-
35
0.874
0.9852
−1% 



adduct-of-Formate-dimer


16016
Metabolite - 3994
35
0.7041
0.9851
−8% 


16071
Metabolite - 4020
50
0.3935
0.9478
5%


16091
Metabolite - 4031-possible-
35
0.94
0.9993
−1% 



norlevorphenol-



isobutylphendienamide-



amprolium


16107
lysine
50
0.8238
0.9851
2%


16137
Metabolite - 4078
35
0.5038
0.9851
−12% 


16161
gamma - glutamyl-glutamic
35
0.5112
0.9851
8%



acid


16186
Metabolite - 4096-possible-
35
0.2257
0.9478
18% 



gamma - glu-gly-leu-


16226
Isobar-28-includes-L-
35
0.6861
0.9851
3%



threonine-L-allothreonine-L-



homoserine-S-4-amino-2-



hydroxybutyric acid


16231
Isobar-20-includes-fumaric
35
0.2502
0.9478
18% 



acid-3-methyl-2-oxobutanoate


16232
Isobar-17-includes-arginine-N-
35
0.9455
0.9993
−1% 



alpha - acetyl-ornithine


16233
Isobar-13-includes-5-keto-D-
35
0.799
0.9851
3%



gluconic acid-2-keto-L-gulonic



acid-D-glucuronic acid-D-



galacturonic acid


16235
Isobar-19-includes-D-saccharic
35
0.8329
0.9851
3%



acid-1-5-anhydro-D-glucitol-2-



deoxy-D-galactose-2-deoxy-D-



glucose-L-fucose-L-rhamnose


16237
Isobar-25-includes-L-gulono-1-
35
0.8393
0.9851
−3% 



4-lactone-glucono-gamma -



lactone-


16241
Isobar-30-includes-
35
0.282
0.9478
11% 



maltotetraose-stachyose


16243
L-kynurenine
35
0.6848
0.9851
2%


16244
Isobar-21-includes-gamma -
35
0.0676
0.7493
−21% 



aminobutyryl-L-histidine-L-



anserine


16246
Isobar-18-includes-D-fructose-
35
0.6754
0.9851
5%



1-phosphate-beta - D-fructose-



6-phosphate


16279
Isobar-36-includes-D-sorbitol-
35
0.0432
0.7407
18% 



6-phosphate-mannitol-1-



phosphate


16290
Metabolite - 4133
50
0.1746
0.9478
−9% 


16308
Metabolite - 4147
50
0.6922
0.9851
−4% 


16330
Metabolite - 4163
35
0.4304
0.9478
−10% 


16337
Metabolite - 4167
35
0.7076
0.9851
−3% 


16462
Metabolite - 4234
35
0.4466
0.9478
−5% 


16471
Metabolite - 4238
35
0.5384
0.9851
10% 


16508
Metabolite - 4272
50
0.1526
0.9478
−11% 


16621
Metabolite - 4355
50
0.3937
0.9478
−17% 


16653
Metabolite - 4361
50
0.0994
0.9247
21% 


16666
Metabolite - 4365
50
0.2946
0.9478
−10% 


16824
iminodiacetic acid
50
0.7755
0.9851
−3% 


16829
Metabolite - 4503
50
0.9392
0.9993
−1% 


16848
Metabolite - 4511
50
0.8497
0.9851
−2% 


16952
Metabolite - 4593
50
0.3035
0.9478
4%


17028
Metabolite - 4611
50
0.3813
0.9478
−5% 


17328
Metabolite - 4768
50
0.4803
0.9659
13% 


17330
Metabolite - 4769
50
0.2485
0.9478
14% 


17359
Metabolite - 4791
50
0.8127
0.9851
−5% 


17388
Metabolite - 4795
50
0.2822
0.9478
11% 


17614
Metabolite - 4966
50
0.33
0.9478
9%


17627
Metabolite - 4986
50
0.0582
0.7407
28% 


18118
Metabolite - 5346
50
0.4123
0.9478
6%


18146
Metabolite - 5366
50
0.0108
0.5749
40% 


18232
Metabolite - 5403
50
0.3291
0.9478
6%


18316
Metabolite - 5437
50
0.1177
0.9478
30% 


18335
D-quinic acid
50
0.6344
0.9851
10% 


18349
DL-indole-3-lactic acid
50
0.6042
0.9851
−4% 


18868
Metabolite - 5847
50
0.8544
0.9851
3%


18926
Metabolite - 5906
50
0.9154
0.9993
4%


18929
Metabolite - 5907
50
0.2112
0.9478
8%
















TABLE 7







Plasma Metabolite Biomarkers to distinguish Non-cancer from Higher


Grade PCA.

















% Change


COMP_ID
COMPOUND
LIB_ID
p-value
q-value
in PCA















53
glutamine
50
0.1993
0.3977
−14%


54
tryptophan
50
0.1049
0.3151
−10%


57
glutamic acid
50
0.1716
0.3828
−18%


59
histidine
50
0.2197
0.4209
−11%


60
leucine
50
0.0833
0.2916
−13%


63
cholesterol
50
0.1481
0.3699
−10%


64
phenylalanine
35
0.05
0.245
−7%


513
creatinine
35
0.0563
0.2564
−10%


527
lactate
50
0.0035
0.0655
−15%


528
alpha-keto-glutarate
35
0.0099
0.0976
−45%


541
4-hydroxyphenylacetate
35
0.3644
0.481
−5%


542
3-hydroxybutanoic acid
50
0.0434
0.221
−45%


569
caffeine
35
0.0049
0.0777
−51%


577
fructose
50
0.0544
0.2523
−41%


581
glucose
50
0.1835
0.3851
−6%


584
mannose
50
0.9521
0.6641
0%


594
niacinamide
35
0.6135
0.59
−11%


597
phosphoenolpyruvate
35
0.4146
0.5151
−9%


1105
linoleic acid
50
0.0622
0.2681
−14%


1107
allantoin
50
0.4785
0.5344
−14%


1110
arachidonic acid
50
0.3429
0.481
−12%


1121
heptadecanoic acid
50
0.0029
0.0624
−19%


1123
inosine
35
0.7999
0.6385
10%


1125
isoleucine
50
0.072
0.2829
−13%


1126
alanine
50
0.0821
0.2916
−16%


1284
threonine
50
0.2588
0.4682
−9%


1299
tyrosine
50
0.6026
0.5883
−4%


1302
methionine
35
0.499
0.5413
−4%


1303
malic acid
35
0.343
0.481
−21%


1336
n-hexadecanoic acid
50
0.0078
0.0976
−16%


1358
octadecanoic acid
50
0.0337
0.1829
−10%


1365
tetradecanoic acid
50
0.0076
0.0976
−17%


1366
trans-4-hydroxyproline
50
0.0164
0.1319
−14%


1413
3-hydroxyphenylacetate
35
0.9038
0.6568
−1%


1414
3-phospho-d-glycerate
35
0.3849
0.4882
−13%


1415
4-amino-5-methyl-2-1H-
35
0.4688
0.5282
−8%



pyrimidinone


1431
(p-Hydroxyphenyl)lactic acid
50
0.0618
0.2681
−22%


1432
alphahydroxybenzeneacetic acid
35
0.9337
0.6641
1%


1437
succinate
50
0.3397
0.481
7%


1444
DL-pipecolic acid
35
0.3851
0.4882
−10%


1480
guanidineacetic acid
35
0.7214
0.6178
5%


1493
ornithine
50
0.1892
0.3889
−18%


1494
5-oxoproline
50
0.1956
0.3977
−9%


1498
N-6-trimethyl-l-lysine
35
0.6864
0.6107
−6%


1507
palmitoleic acid
50
4.00E−04
0.0178
−40%


1508
pantothenic acid
35
0.3718
0.481
−17%


1519
sucrose
50
0.8433
0.6512
4%


1557
3-methylglutaric acid
35
0.0249
0.1479
−18%


1561
alpha-tocopherol
50
0.0158
0.1319
−53%


1564
citric acid
50
0.4573
0.5239
−4%


1570
oleic acid
50
0.0021
0.0503
−35%


1572
glyceric acid
50
0.1532
0.3719
20%


1574
histamine
35
0.8493
0.6519
4%


1584
methyl-indole-3-acetate
35
0.28
0.4695
−13%


1587
N-acetyl-L-leucine
35
0.71
0.6136
−10%


1591
N-acetyl-L-valine
35
0.0093
0.0976
21%


1604
uric acid
35
0.7956
0.6385
−1%


1643
fumaric acid
50
0.4015
0.5016
−9%


1645
n-dodecanoate
50
0.187
0.3875
−12%


1648
serine
50
0.3365
0.481
−7%


1649
valine
50
0.0224
0.1466
−14%


1670
urea
50
0.3643
0.481
7%


1708
7-8-dihydrofolic acid
35
0.9239
0.6628
4%


1898
proline
50
0.1339
0.3538
−19%


2078
pyrophosphate
35
0.7732
0.6377
−7%


2092
catechol
35
0.259
0.4682
−31%


2132
citrulline
50
0.4546
0.5239
6%


2730
gamma-L-glutamyl-L-
35
0.552
0.5628
12%



glutamine


2734
gamma-L-glutamyl-L-tyrosine
35
0.5344
0.5577
4%


2832
adenosine-5-monophosphate
35
0.1631
0.3779
−17%


2848
guanosine-5-diphosphate
35
0.5329
0.5577
−8%


3127
hypoxanthine
35
0.7241
0.6178
−5%


3138
pyridoxamine-phosphate
35
0.8654
0.6522
2%


3147
xanthine
35
0.9538
0.6641
2%


4966
xylitol
35
0.3179
0.481
18%


5280
biliverdin
35
0.4282
0.5189
−11%


5331
pyridoxal-phosphate
35
0.3699
0.481
4%


5618
Metabolite - 1085-possible-
35
0.0247
0.1479
21%



isolobinine-or-4-aminoestra-1-



3-5-10-triene-3-17beta-diol


5628
Metabolite - 1086
35
0.5566
0.5628
−10%


5669
Metabolite - 1104
35
0.0086
0.0976
−15%


5687
Metabolite - 1110
35
0.2792
0.4695
45%


5689
Metabolite - 1111-possible-
35
0.9467
0.6641
1%



methylnitronitrosoguanidine-or-



ethyl-thiocarbamoylacetate


5697
acetylcarnitine-
35
0.2254
0.4256
−12%


5717
Metabolite - 1121
35
0.0166
0.1319
29%


5733
Metabolite - 1127
35
6.00E−04
0.0178
−35%


5765
Metabolite - 1142-possible-5-
35
0.611
0.59
−11%



hydroxypentanoate-or-beta-



hydroxyisovaleric acid


5788
Metabolite - 1183
35
0.7587
0.6319
10%


5792
Metabolite - 1185
35
0.0012
0.034
68%


5800
Metabolite - 1188
35
0.2872
0.4722
18%


6112
Metabolite - 1203-HXGXX-in-
35
0.3875
0.4889
−20%



MTRX


6130
Metabolite - 1208
35
0.5109
0.547
−15%


6136
Metabolite - 1211-possible-
35
0.2482
0.4551
204%



IHWESASLLR-


6144
Metabolite - 1215
35
0.7273
0.6178
12%


6147
Metabolite - 1216
35
0.4342
0.5189
−8%


6155
Metabolite - 1220
35
0.8726
0.6522
3%


6171
Metabolite - 1244
35
0.7307
0.6186
−6%


6266
Metabolite - 1286
35
0.021
0.1462
16%


6278
Metabolite - 1289
35
0.8015
0.6385
−4%


6362
Metabolite - 1323-possible-p-
35
0.5645
0.5664
17%



cresol-sulfate


6398
Metabolite - 1335
35
0.9375
0.6641
1%


6413
Metabolite - 1342-possible-
35
0.7405
0.6228
7%



phenylacetylglutamine-or-



formyl-N-acetyl-5-



methoxykynurenamine


6437
Metabolite - 1349-possible-N-
35
0.9989
0.6849
0%



acetyl-8-O-methyl-Neuraminic



acid


6443
Metabolite - 1351
35
0.7988
0.6385
−3%


6537
Metabolite - 1389-possible-
35
0.5683
0.5664
−11%



gemfibrozil-glucuronide-


6549
Metabolite - 1392
35
0.8385
0.6512
−5%


6787
Metabolite - 1465
35
0.7433
0.6231
−4%


6852
Metabolite - 1498
35
0.3324
0.481
15%


6987
Metabolite - 1573
35
0.8266
0.6482
−4%


7029
Metabolite - 1597
35
0.6293
0.6006
3%


7081
Metabolite - 1609
35
0.118
0.327
−16%


7177
Metabolite - 1656
35
0.3641
0.481
15%


7359
n-acetyl-L-aspartic acid
35
0.0139
0.1266
−23%


7446
p-hydroxybenzaldehyde
35
0.3129
0.481
−9%


7595
Metabolite - 1817
35
0.0951
0.3035
24%


7639
oxalic acid
35
0.0942
0.3035
14%


7644
Metabolite - 1831-possible-Cl-
35
0.026
0.1507
−61%



adduct-of-citrulline


7650
Metabolite - 1834
35
0.0722
0.2829
−35%


7652
Metabolite - 1835
35
0.4205
0.5151
11%


7654
Metabolite - 1836
35
0.0891
0.295
−28%


7660
Metabolite - 1839
35
0.0218
0.1462
−45%


7672
Metabolite - 1843
35
0.9787
0.6778
−1%


7933
Metabolite - 1911
35
0.4204
0.5151
25%


7935
paraxanthine
35
0.0203
0.1462
−41%


7941
Metabolite - 1914
35
0.3503
0.481
32%


7944
Metabolite - 1915
35
0.8018
0.6385
15%


7957
trans-2-3-4-trimethoxycinnamic
35
0.3149
0.481
35%



acid


8091
glycocholic acid
35
0.9047
0.6568
−5%


8176
Metabolite - 1974
35
0.8572
0.6522
4%


8189
Metabolite - 1977
35
0.1838
0.3851
−12%


8196
Metabolite - 1979-Cl-adduct-of-
35
0.9459
0.6641
1%



isobar-19


8217
Metabolite - 1983
35
0.3016
0.481
246%


8300
Metabolite - 1988
35
0.01
0.0976
−30%


8336
Metabolite - 2005
35
0.0359
0.1905
−26%


8404
Metabolite - 2027
35
0.1676
0.3788
−14%


8649
Metabolite - 2053
35
0.7092
0.6136
−5%


8669
Metabolite - 2055
35
0.8342
0.6512
4%


8677
Metabolite - 2056
35
0.1623
0.3779
−15%


8796
Metabolite - 2074
35
0.9322
0.6641
2%


8959
Metabolite - 2100
35
0.6011
0.5883
4%


9007
Metabolite - 2108
35
0.0055
0.0777
−29%


9024
Metabolite - 2111
35
0.3265
0.481
−15%


9092
Metabolite - 2129
35
0.8607
0.6522
−4%


9106
Metabolite - 2130
35
0.0964
0.3035
72%


9130
Metabolite - 2139
35
0.5099
0.547
7%


9137
Metabolite - 2141
35
0.0052
0.0777
−43%


9491
Metabolite - 2185
35
0.6878
0.6107
4%


9748
Metabolite - 2212
35
0.2255
0.4256
19%


10087
Metabolite - 2249
35
0.6409
0.6006
−6%


10092
Metabolite - 2250
35
0.4987
0.5413
18%


10122
Metabolite - 2254
35
0.1171
0.327
−39%


10143
Metabolite - 2255-
35
0.1844
0.3851
139%



hydroxyproline-form-of-



bradykinin


10145
Metabolite - 2256
35
0.862
0.6522
−3%


10245
Metabolite - 2269-
35
0.2698
0.4695
34%


10317
Metabolite - 2279
35
0.3109
0.481
−24%


10327
Metabolite - 2281
35
0.4355
0.5189
−24%


10378
Metabolite - 2287
35
0.1438
0.3664
346%


10438
gamma-glu-leu
35
0.4822
0.5344
−6%


10461
Metabolite - 2313
35
0.5649
0.5664
−6%


10476
Metabolite - 2316
35
0.2043
0.4036
51%


10544
Metabolite - 2329
35
1.00E−04
0.0086
−42%


10551
Metabolite - 2347
35
0.3563
0.481
30%


10604
Metabolite - 2370
35
0.8174
0.6449
4%


10629
Metabolite - 2386
35
0.516
0.5502
−14%


10644
Metabolite - 2387
35
0.5362
0.5577
−32%


10655
Metabolite - 2388
35
0.1466
0.3699
11%


10667
Metabolite - 2389
35
0.0776
0.291
186%


10672
Metabolite - 2390
35
0.0718
0.2829
−27%


10692
Metabolite - 2391
35
0.0982
0.3052
−12%


10698
Metabolite - 2392
35
0.6996
0.6131
−15%


10737
Isobar-1-includes-mannose-
35
0.8978
0.6568
−2%



fructose-glucose-galactose-alpha-



L-sorbopyranose-Inositol-D-



allose-D--altrose-D-psicone


10739
Metabolite - 2407
35
0.0093
0.0976
48%


10741
Isobar-2-includes-2-
35
0.5412
0.5606
−15%



aminoisobutyric acid-3-amino-



isobutyrate-2-amino-butyrate-4-



aminobutanoic acid-



dimethylglycine-choline-


10743
Isobar-4-includes-Gluconic
35
0.3542
0.481
14%



acid-DL-arabinose-D-ribose-L-



xylose-DL-lyxose-D-xylulose


10744
Isobar-5-includes-asparagine-
35
0.1653
0.3788
17%



ornithine-gly-gly


10746
Isobar-6-includes-valine-betaine
35
0.0606
0.2681
−8%


10753
Isobar-9-includes-galactinol-
35
0.7716
0.6377
−6%



dihydrate-turanose-kojibiose-D-



leucrose-lactulose-sophorose-



sucrose-beta-D-lactose-D-



trehalose-D-cellobiose-D-



Maltose-palatinose-melibiose-



alpha-D-lactose


10782
Metabolite - 2486
35
0.6665
0.6048
−8%


10785
Metabolite - 2506
35
0.1515
0.3712
−39%


10787
Metabolite - 2507
35
0.2156
0.4171
−34%


10825
Metabolite - 2546
35
0.4358
0.5189
−13%


11053
Metabolite - 2567
35
0.5492
0.5628
6%


11111
Metabolite - 2592
35
0.3309
0.481
−41%


11219
Metabolite - 2686
35
0.9155
0.6628
1%


11222
Metabolite - 2688
35
0.6923
0.6112
6%


11323
Metabolite - 2711
35
0.0036
0.0655
−21%


11438
phosphate
50
0.9259
0.6628
−1%


11499
Metabolite - 2753
35
0.6692
0.6048
−5%


11777
glycine
50
0.1082
0.3168
−16%


11813
Metabolite - 2809
35
0.7365
0.6215
−7%


12035
nonanate
50
0.4925
0.5413
3%


12109
Metabolite - 2853
35
0.6348
0.6006
−8%


12298
Metabolite - 2867
35
0.1809
0.3851
−47%


12444
Metabolite - 2888-possible-
35
0.3955
0.4965
13%



sulfated-Rosiglitazone


12478
Metabolite - 2898
35
0.2404
0.4472
−36%


12532
Metabolite - 2914
50
0.2774
0.4695
2%


12533
Metabolite - 2915
50
0.4585
0.5239
7%


12543
2-hydroxy-butanoic acid
50
0.1732
0.3828
−17%


12562
Metabolite - 2955
50
0.8848
0.6555
1%


12593
Metabolite - 2973
50
0.8416
0.6512
1%


12594
Metabolite - 2974
50
0.1138
0.3224
11%


12601
Metabolite - 2978
50
0.0765
0.291
23%


12625
Metabolite - 3002
50
0.0539
0.2523
−21%


12626
Metabolite - 3003
50
0.9736
0.6761
0%


12627
Metabolite - 3004
50
0.9538
0.6641
−1%


12639
Metabolite - 3012
50
0.384
0.4882
7%


12641
meso-erythritol
50
0.1016
0.3119
−16%


12644
Metabolite - 3016
50
0.1504
0.3712
−9%


12645
Metabolite - 3017
50
0.2449
0.4523
15%


12647
Metabolite - 3019
50
0.232
0.4348
11%


12648
Metabolite - 3020
50
0.5697
0.5664
7%


12650
Metabolite - 3022
50
0.6591
0.6042
5%


12656
Metabolite - 3025
50
0.3225
0.481
9%


12658
Metabolite - 3026
50
0.321
0.481
10%


12663
Metabolite - 3030
50
0.0082
0.0976
22%


12666
Metabolite - 3033
50
0.0244
0.1479
14%


12673
Metabolite - 3040
50
0.0517
0.2487
27%


12682
Metabolite - 3044
35
0.5288
0.5577
−8%


12719
Metabolite - 3055
35
0.4505
0.5239
21%


12720
Metabolite - 3056
35
0.7025
0.6131
−3%


12726
Metabolite - 3058
50
0.4992
0.5413
12%


12739
1-5-anhydro-D-glucitol
50
0.3236
0.481
−12%


12751
Metabolite - 3073
50
0.1743
0.3828
23%


12753
Metabolite - 3074
50
0.136
0.3538
−39%


12754
Metabolite - 3075
50
0.6421
0.6006
6%


12756
Metabolite - 3077
50
0.5522
0.5628
6%


12757
Metabolite - 3078
50
0.4196
0.5151
9%


12761
Metabolite - 3081
50
0.4686
0.5282
−8%


12765
inositol
50
0.2758
0.4695
−12%


12768
Metabolite - 3088
50
0.0202
0.1462
38%


12769
Metabolite - 3089
50
0.2713
0.4695
−14%


12771
Metabolite - 3091
50
0.2132
0.4171
48%


12773
Metabolite - 3093
50
0.7501
0.6267
−5%


12774
Metabolite - 3094
50
0.5302
0.5577
−7%


12777
Metabolite - 3097
50
0.9998
0.6849
0%


12780
Metabolite - 3098
50
0.0769
0.291
31%


12781
Metabolite - 3099
50
0.8957
0.6568
2%


12784
Metabolite - 3102
50
0.3579
0.481
−7%


12790
Metabolite - 3108
50
0.8722
0.6522
1%


12876
Metabolite - 3125
35
0.4287
0.5189
−6%


12912
Metabolite - 3129
35
0.9973
0.6849
0%


12924
Metabolite - 3131
35
0.2901
0.4739
29%


12931
DL-hexanoyl-carnitine
35
0.7104
0.6136
−3%


12960
Metabolite - 3134
35
0.6932
0.6112
−11%


12969
Metabolite - 3135
35
0.7666
0.6364
10%


13018
Metabolite - 3138
35
0.1116
0.3215
−20%


13038
Metabolite - 3143
35
0.1583
0.3769
−17%


13065
Metabolite - 3146
35
0.0835
0.2916
−33%


13104
Metabolite - 3160
35
0.1779
0.3843
−15%


13142
Metabolite - 3165
35
0.2842
0.4702
−7%


13146
Metabolite - 3166
35
0.9041
0.6568
−3%


13148
Metabolite - 3167
35
0.9239
0.6628
1%


13179
possible-Metabolite - 3176-
35
0.1352
0.3538
28%



possible-creatine


13208
Metabolite - 3181
35
0.5937
0.5841
−6%


13211
Metabolite - 3182
35
0.649
0.6015
11%


13214
Metabolite - 3183-possible-
35
0.946
0.6641
1%



gamma-L-glutamyl-L-



phenylalanine


13217
Metabolite - 3184
35
0.3141
0.481
−13%


13249
Metabolite - 3215
35
0.2706
0.4695
−13%


13251
Metabolite - 3216
35
0.2161
0.4171
−16%


13257
Metabolite - 3218
35
0.8158
0.6449
−4%


13342
Metabolite - 3243
35
0.9895
0.6834
0%


13448
Metabolite - 3303
35
0.0146
0.128
−17%


13459
Metabolite - 3305
35
1.00E−04
0.0086
−59%


13484
Metabolite - 3309
35
0.0639
0.2681
−27%


13505
Metabolite - 3313
35
0.3298
0.481
−38%


13509
Metabolite - 3314
35
0.1312
0.3519
−19%


13534
Metabolite - 3320-possible-
35
0.556
0.5628
−21%



pimpinellin-or-



tetrahydroxybenzophenone


13545
Metabolite - 3322
35
5.00E−04
0.0178
−39%


13589
Metabolite - 3327
35
5.00E−04
0.0178
−52%


13775
Metabolite - 3370
35
0.4705
0.5282
−7%


13803
Metabolite - 3377
35
0
0.0026
−64%


13904
Metabolite - 3402
35
0.0047
0.0777
−38%


14027
Metabolite - 3426
35
0.5712
0.5664
−2%


14084
Metabolite - 3436
35
0.8882
0.6558
2%


14117
Metabolite - 3441
35
0.4955
0.5413
−6%


14239
Metabolite - 3474
35
0.168
0.3788
20%


14249
Metabolite - 3476
35
0.7254
0.6178
−8%


14368
Metabolite - 3489
35
0.1059
0.3151
−35%


14439
Metabolite - 3498
35
0.4571
0.5239
9%


14495
Metabolite - 3534
35
0.1123
0.3215
−23%


14595
Metabolite - 3576
35
0.3216
0.481
19%


14608
Metabolite - 3578
35
0.3148
0.481
23%


14639
Metabolite - 3603
35
0.0022
0.0503
40%


14640
Metabolite - 3604
35
0.6656
0.6048
12%


14672
Metabolite - 3615
35
0.8695
0.6522
3%


14715
Metabolite - 3653-possible-
35
0.7021
0.6131
13%



stachydrine-


14766
Metabolite - 3670
35
0.5739
0.5668
−5%


14785
isobar-glycochenodeoxycholic
35
0.6413
0.6006
−12%



acid-glycodeoxycholic acid


14787
Metabolite - 3698
35
0.798
0.6385
−4%


14837
Metabolite - 3707
35
0.0965
0.3035
108%


14961
Metabolite - 3752
35
0.2823
0.4701
145%


15000
Metabolite - 3758
35
0.123
0.3334
−38%


15017
Metabolite - 3761
35
0.8844
0.6555
−2%


15032
Metabolite - 3765
35
0.6458
0.6006
−11%


15063
Metabolite - 3772
35
0.0788
0.291
−15%


15113
Metabolite - 3783
35
0.4349
0.5189
12%


15122
glycerol
50
0.0247
0.1479
−14%


15128
DL-homocysteine
35
0.3684
0.481
−11%


15129
D-alanyl-D-alanine
35
0.8683
0.6522
−2%


15211
Metabolite - 3807
35
0.2961
0.4806
−6%


15220
Metabolite - 3813
35
0.0871
0.295
−23%


15227
Metabolite - 3816
35
0.8378
0.6512
−3%


15251
Metabolite - 3830
35
0.0863
0.295
−24%


15253
Metabolite - 3832-possible-
35
0.0475
0.2374
−49%



phenol-sulfate


15278
Metabolite - 3843
35
0.0309
0.1711
−17%


15319
DL-phenyllactic acid
35
0.2786
0.4695
−22%


15326
Metabolite - 3879
35
0.6363
0.6006
28%


15328
azelaic acid
35
0.1571
0.3769
−10%


15336
tartaric acid
35
0.0214
0.1462
−38%


15365
sn-Glycerol-3-phosphate
50
0.5069
0.547
−5%


15389
Metabolite - 3900
35
0.0294
0.1667
−14%


15500
carnitine
35
0.197
0.3977
10%


15529
Metabolite - 3951
35
0.6687
0.6048
−3%


15535
Metabolite - 3955
35
0.4421
0.5216
27%


15606
Metabolite - 3968
35
0.8468
0.6519
−4%


15612
Metabolite - 3972
35
0.3503
0.481
11%


15626
Metabolite - 3977
35
0.0207
0.1462
−17%


15677
3-methyl-L-histidine
35
0.3568
0.481
−6%


15681
4-Guanidinobutanoic acid
35
0.8904
0.6558
−2%


15683
4-methyl-2-oxopentanoate
50
0.1063
0.3151
−16%


15704
heptanedioic acid
35
0.1218
0.3334
47%


15744
N-N-dimethylarginine
35
0.3455
0.481
−8%


15753
hippuric acid
35
0.6581
0.6042
−9%


15991
L-alpha-
35
0.3514
0.481
−18%



glycerophosphorylcholine


16002
Metabolite - 3992-possible-Cl-
35
0.643
0.6006
3%



adduct-of-Formate-dimer


16016
Metabolite - 3994
35
0.7835
0.6385
−8%


16071
Metabolite - 4020
50
0.7967
0.6385
−1%


16091
Metabolite - 4031-possible-
35
0.0804
0.2916
−12%



norlevorphenol-



isobutylphendienamide-



amprolium


16107
lysine
50
0.1771
0.3843
−12%


16137
Metabolite - 4078
35
0.2647
0.4695
−19%


16161
gamma-glutamyl-glutamic acid
35
0.9512
0.6641
0%


16186
Metabolite - 4096-possible-
35
0.4824
0.5344
19%



gamma-glu-gly-leu-


16226
Isobar-28-includes-L-threonine-
35
0.1998
0.3977
14%



L-allothreonine-L-homoserine-



S-4-amino-2-hydroxybutyric



acid


16231
Isobar-20-includes-fumaric
35
0.5237
0.5561
12%



acid-3-methyl-2-oxobutanoate


16232
Isobar-17-includes-arginine-N-
35
0.0125
0.1175
36%



alpha-acetyl-ornithine


16233
Isobar-13-includes-5-keto-D-
35
0.1598
0.3771
−19%



gluconic acid-2-keto-L-gulonic



acid-D-glucuronic acid-D-



galacturonic acid


16235
Isobar-19-includes-D-saccharic
35
0.5502
0.5628
11%



acid-1-5-anhydro-D-glucitol-2-



deoxy-D-galactose-2-deoxy-D-



glucose-L-fucose-L-rhamnose


16237
Isobar-25-includes-L-gulono-1-
35
0.7148
0.6154
−8%



4-lactone-glucono-gamma-



lactone-


16241
Isobar-30-includes-
35
0.6804
0.6106
−6%



maltotetraose-stachyose


16243
L-kynurenine
35
0.7838
0.6385
−3%


16244
Isobar-21-includes-gamma-
35
0.6805
0.6106
7%



aminobutyryl-L-histidine-L-



anserine


16246
Isobar-18-includes-D-fructose-
35
0.8566
0.6522
4%



1-phosphate-beta-D-fructose-6-



phosphate


16279
Isobar-36-includes-D-sorbitol-6-
35
0.3438
0.481
−13%



phosphate-mannitol-1-phosphate


16290
Metabolite - 4133
50
0.6833
0.6107
5%


16308
Metabolite - 4147
50
0.0642
0.2681
−24%


16330
Metabolite - 4163
35
0.4532
0.5239
−12%


16337
Metabolite - 4167
35
0.2792
0.4695
−17%


16462
Metabolite - 4234
35
0.4546
0.5239
−8%


16471
Metabolite - 4238
35
0.9246
0.6628
2%


16508
Metabolite - 4272
50
0.3504
0.481
−12%


16621
Metabolite - 4355
50
0.3773
0.4856
−17%


16653
Metabolite - 4361
50
0.3706
0.481
17%


16666
Metabolite - 4365
50
0.7897
0.6385
−4%


16824
iminodiacetic acid
50
0.041
0.213
−26%


16829
Metabolite - 4503
50
0.8049
0.639
−7%


16848
Metabolite - 4511
50
0.0692
0.2829
−25%


16952
Metabolite - 4593
50
0.6542
0.604
2%


17028
Metabolite - 4611
50
0.3655
0.481
−6%


17328
Metabolite - 4768
50
0.7791
0.6385
−7%


17330
Metabolite - 4769
50
0.1385
0.3566
17%


17359
Metabolite - 4791
50
0.8812
0.6555
−5%


17388
Metabolite - 4795
50
0.3033
0.481
22%


17614
Metabolite - 4966
50
0.3248
0.481
11%


17627
Metabolite - 4986
50
0.6096
0.59
12%


18118
Metabolite - 5346
50
0.6124
0.59
−6%


18146
Metabolite - 5366
50
0.6449
0.6006
7%


18232
Metabolite - 5403
50
0.2718
0.4695
10%


18316
Metabolite - 5437
50
0.4383
0.5195
−19%


18335
D-quinic acid
50
0.0891
0.295
−42%


18349
DL-indole-3-lactic acid
50
5.00E−04
0.0178
−25%


18868
Metabolite - 5847
50
0.4666
0.5282
−15%


18926
Metabolite - 5906
50
0.3425
0.481
−27%


18929
Metabolite - 5907
50
0.8229
0.6473
2%
















TABLE 8







Plasma Metabolite Biomarkers to distinguish Lower Grade PCA from


Higher Grade PCA.

















% Change







in Higher


COMP_ID
COMPOUND
LIB_ID
p-value
q-value
PCA















53
glutamine
50
0.2081
0.4944
−13%


54
tryptophan
50
0.0734
0.3431
−13%


57
glutamic acid
50
0.3386
0.6063
−13%


59
histidine
50
0.742
0.7437
−3%


60
leucine
50
0.015
0.154
−19%


63
cholesterol
50
0.19
0.4682
−9%


64
phenylalanine
35
0.1602
0.4579
−5%


513
creatinine
35
0.9764
0.7893
0%


527
lactate
50
0.0062
0.0915
−14%


528
alpha-keto-glutarate
35
0.6988
0.7368
−9%


541
4-hydroxyphenylacetate
35
0.9884
0.7893
0%


542
3-hydroxybutanoic acid
50
0.1111
0.4081
−50%


569
caffeine
35
6.00E−04
0.0433
−70%


577
fructose
50
0.0966
0.3887
−20%


581
glucose
50
0.6171
0.7298
−2%


584
mannose
50
0.9074
0.7713
−1%


594
niacinamide
35
0.4972
0.666
−18%


597
phosphoenolpyruvate
35
0.7347
0.7434
−4%


1105
linoleic acid
50
0.0404
0.2538
−17%


1107
allantoin
50
0.7673
0.7448
−6%


1110
arachidonic acid
50
0.6643
0.7368
−6%


1121
heptadecanoic acid
50
0
0.0036
−27%


1123
inosine
35
0.972
0.7891
1%


1125
isoleucine
50
0.0129
0.1407
−19%


1126
alanine
50
0.0951
0.3887
−15%


1284
threonine
50
0.3138
0.5918
−8%


1299
tyrosine
50
0.1559
0.4579
−11%


1302
methionine
35
0.5223
0.687
−4%


1303
malic acid
35
0.5527
0.712
−13%


1336
n-hexadecanoic acid
50
0.0024
0.0649
−20%


1358
octadecanoic acid
50
9.00E−04
0.0464
−16%


1365
tetradecanoic acid
50
0.0017
0.0613
−22%


1366
trans-4-hydroxyproline
50
0.0035
0.0738
−15%


1413
3-hydroxyphenylacetate
35
0.6788
0.7368
2%


1414
3-phospho-d-glycerate
35
0.4156
0.6338
−12%


1415
4-amino-5-methyl-2-1H-
35
0.3
0.5825
−10%



pyrimidinone


1431
(p-Hydroxyphenyl)lactic
50
0.0035
0.0738
−27%



acid


1432
alphahydroxybenzeneacetic
35
0.8113
0.751
3%



acid


1437
succinate
50
0.2184
0.5028
9%


1444
DL-pipecolic acid
35
0.9642
0.7862
0%


1480
guanidineacetic acid
35
0.8726
0.7585
−2%


1493
ornithine
50
0.1811
0.4682
−19%


1494
5-oxoproline
50
0.0231
0.2124
−12%


1498
N-6-trimethyl-l-lysine
35
0.7026
0.7368
5%


1507
palmitoleic acid
50
7.00E−04
0.0433
−44%


1508
pantothenic acid
35
0.182
0.4682
−31%


1519
sucrose
50
0.9548
0.7862
−2%


1557
3-methylglutaric acid
35
0.19
0.4682
−10%


1561
alpha-tocopherol
50
0.8757
0.759
−6%


1564
citric acid
50
0.2758
0.5606
−6%


1570
oleic acid
50
0.0045
0.0866
−34%


1572
glyceric acid
50
0.2114
0.4945
17%


1574
histamine
35
0.8416
0.7585
−4%


1584
methyl-indole-3-acetate
35
0.2877
0.569
−13%


1587
N-acetyl-L-leucine
35
0.2729
0.5593
−31%


1591
N-acetyl-L-valine
35
0.9102
0.7713
1%


1604
uric acid
35
0.813
0.751
−1%


1643
fumaric acid
50
0.5872
0.7241
−6%


1645
n-dodecanoate
50
0.1214
0.4111
−15%


1648
serine
50
0.0574
0.3133
−14%


1649
valine
50
0.0074
0.1041
−19%


1670
urea
50
0.6012
0.7257
3%


1708
7-8-dihydrofolic acid
35
0.5075
0.673
−20%


1898
proline
50
0.221
0.5048
−16%


2078
pyrophosphate
35
0.7583
0.7448
−7%


2092
catechol
35
0.2733
0.5593
−31%


2132
citrulline
50
0.3254
0.5955
9%


2730
gamma-L-glutamyl-L-
35
0.4725
0.6556
16%



glutamine


2734
gamma-L-glutamyl-L-
35
0.7177
0.7423
−2%



tyrosine


2832
adenosine-5-monophosphate
35
0.3158
0.5918
−14%


2848
guanosine-5-diphosphate
35
0.445
0.6491
−9%


3127
hypoxanthine
35
0.948
0.7855
1%


3138
pyridoxamine-phosphate
35
0.4558
0.6552
−12%


3147
xanthine
35
0.6472
0.73
13%


4966
xylitol
35
0.463
0.6556
13%


5280
biliverdin
35
0.1482
0.4503
−33%


5331
pyridoxal-phosphate
35
0.0379
0.2538
9%


5618
Metabolite - 1085-possible-
35
0.0709
0.3425
16%



isolobinine-or-4-aminoestra-



1-3-5-10-triene-3-17beta-



diol


5628
Metabolite - 1086
35
0.6001
0.7257
−8%


5669
Metabolite - 1104
35
0.0196
0.1865
−14%


5687
Metabolite - 1110
35
0.3645
0.6113
37%


5689
Metabolite - 1111-possible-
35
0.4217
0.6338
−9%



methylnitronitrosoguanidine-



or-ethyl-



thiocarbamoylacetate


5697
acetylcarnitine-
35
0.262
0.559
−11%


5717
Metabolite - 1121
35
0.1136
0.4081
17%


5733
Metabolite - 1127
35
0.0695
0.3413
−20%


5765
Metabolite - 1142-possible-
35
0.5859
0.7241
−18%



5-hydroxypentanoate-or-



beta-hydroxyisovaleric



acid


5788
Metabolite - 1183
35
0.3872
0.6303
−55%


5792
Metabolite - 1185
35
0.0919
0.3869
24%


5800
Metabolite - 1188
35
0.4258
0.6338
−13%


6112
Metabolite - 1203-HXGXA
35
0.1905
0.4682
−48%



in-MTRX


6130
Metabolite - 1208
35
0.3544
0.6113
−20%


6136
Metabolite - 1211-possible-
35
0.6994
0.7368
−22%



IHWESASLLR-


6144
Metabolite - 1215
35
0.7751
0.7448
10%


6147
Metabolite - 1216
35
0.3347
0.6063
−15%


6155
Metabolite - 1220
35
0.9929
0.7893
0%


6171
Metabolite - 1244
35
0.3205
0.5918
−15%


6266
Metabolite - 1286
35
0.1856
0.4682
11%


6278
Metabolite - 1289
35
0.4585
0.6556
14%


6362
Metabolite - 1323-possible-
35
0.9961
0.7893
0%



p-cresol-sulfate


6398
Metabolite - 1335
35
0.8918
0.766
2%


6413
Metabolite - 1342-possible-
35
0.7003
0.7368
−8%



phenylacetylglutamine-or-



formyl-N-acetyl-5-



methoxykynurenamine


6437
Metabolite - 1349-possible-
35
0.9819
0.7893
−1%



N-acetyl-8-O-methyl-



Neuraminic acid


6443
Metabolite - 1351
35
0.871
0.7585
−2%


6537
Metabolite - 1389-possible-
35
0.302
0.5825
−78%



gemfibrozil-glucuronide-


6549
Metabolite - 1392
35
0.4157
0.6338
−15%


6787
Metabolite - 1465
35
0.649
0.73
−8%


6852
Metabolite - 1498
35
0.0777
0.3524
33%


6987
Metabolite - 1573
35
0.9489
0.7855
−1%


7029
Metabolite - 1597
35
0.4038
0.6338
−6%


7081
Metabolite - 1609
35
0.0305
0.2368
−23%


7177
Metabolite - 1656
35
0.4157
0.6338
13%


7359
n-acetyl-L-aspartic acid
35
0.0437
0.2628
−21%


7446
p-hydroxybenzaldehyde
35
0.6766
0.7368
−4%


7595
Metabolite - 1817
35
0.153
0.4554
21%


7639
oxalic acid
35
0.2078
0.4944
11%


7644
Metabolite - 1831-possible-
35
0.0691
0.3413
−44%



Cl-adduct-of-citrulline


7650
Metabolite - 1834
35
0.1156
0.4081
−30%


7652
Metabolite - 1835
35
0.4281
0.6338
−11%


7654
Metabolite - 1836
35
0.147
0.4503
−25%


7660
Metabolite - 1839
35
0.0387
0.2538
−42%


7672
Metabolite - 1843
35
0.7808
0.7448
−3%


7933
Metabolite - 1911
35
0.5335
0.6956
−16%


7935
paraxanthine
35
0.0019
0.0613
−58%


7941
Metabolite - 1914
35
0.4757
0.6556
25%


7944
Metabolite - 1915
35
0.6141
0.7297
−26%


7957
trans-2-3-4-
35
0.4257
0.6338
28%



trimethoxycinnamic acid


8091
glycocholic acid
35
0.4181
0.6338
−27%


8176
Metabolite - 1974
35
0.7599
0.7448
−5%


8189
Metabolite - 1977
35
0.0864
0.3689
−14%


8196
Metabolite - 1979-Cl-
35
0.6427
0.73
6%



adduct-of-isobar-19


8217
Metabolite - 1983
35
0.6235
0.73
−32%


8300
Metabolite - 1988
35
0.0635
0.3225
−19%


8336
Metabolite - 2005
35
0.0395
0.2538
−25%


8404
Metabolite - 2027
35
0.3196
0.5918
−10%


8649
Metabolite - 2053
35
0.1695
0.4624
−19%


8669
Metabolite - 2055
35
0.9053
0.7713
3%


8677
Metabolite - 2056
35
0.0608
0.3144
−20%


8796
Metabolite - 2074
35
0.7798
0.7448
4%


8959
Metabolite - 2100
35
0.9464
0.7855
−1%


9007
Metabolite - 2108
35
0.0164
0.1608
−29%


9024
Metabolite - 2111
35
0.5873
0.7241
−10%


9092
Metabolite - 2129
35
0.8698
0.7585
5%


9106
Metabolite - 2130
35
0.0606
0.3144
95%


9130
Metabolite - 2139
35
0.6874
0.7368
5%


9137
Metabolite - 2141
35
0.0058
0.0915
−49%


9491
Metabolite - 2185
35
0.1596
0.4579
−12%


9748
Metabolite - 2212
35
0.0811
0.355
31%


10087
Metabolite - 2249
35
0.8331
0.7585
−3%


10092
Metabolite - 2250
35
0.2327
0.5235
−27%


10122
Metabolite - 2254
35
0.3765
0.6227
−29%


10143
Metabolite - 2255-
35
0.6393
0.73
27%



hydroxyproline-form-of-



bradykinin


10145
Metabolite - 2256
35
0.4476
0.6495
18%


10245
Metabolite - 2269-
35
0.4123
0.6338
24%


10317
Metabolite - 2279
35
0.0505
0.2916
−42%


10327
Metabolite - 2281
35
0.3395
0.6063
−44%


10378
Metabolite - 2287
35
0.2325
0.5235
180%


10438
gamma-glu-leu
35
0.245
0.5351
−10%


10461
Metabolite - 2313
35
0.7899
0.7448
−3%


10476
Metabolite - 2316
35
0.1189
0.4081
74%


10544
Metabolite - 2329
35
0
0.0014
−42%


10551
Metabolite - 2347
35
0.5251
0.6877
20%


10604
Metabolite - 2370
35
0.9852
0.7893
0%


10629
Metabolite - 2386
35
0.5977
0.7257
−11%


10644
Metabolite - 2387
35
0.3024
0.5825
−55%


10655
Metabolite - 2388
35
0.1144
0.4081
12%


10667
Metabolite - 2389
35
0.1156
0.4081
138%


10672
Metabolite - 2390
35
0.0817
0.355
−41%


10692
Metabolite - 2391
35
0.3467
0.6113
−7%


10698
Metabolite - 2392
35
0.8622
0.7585
−7%


10737
Isobar-1-includes-mannose-
35
0.6822
0.7368
−6%



fructose-glucose-galactose-



alpha-L-sorbopyranose-



Inositol-D-allose-D--altrose-



D-psicone


10739
Metabolite - 2407
35
0.0119
0.1402
48%


10741
Isobar-2-includes-2-
35
0.6689
0.7368
−7%



aminoisobutyric acid-3-



amino-isobutyrate-2-amino-



butyrate-4-aminobutanoic



acid-dimethylglycine-



choline-


10743
Isobar-4-includes-Gluconic
35
0.3076
0.5847
16%



acid-DL-arabinose-D-



ribose-L-xylose-DL-lyxose-



D-xylulose


10744
Isobar-5-includes-
35
0.2642
0.559
13%



asparagine-ornithine-gly-gly


10746
Isobar-6-includes-valine-
35
0.0032
0.0738
−12%



betaine


10753
Isobar-9-includes-
35
0.9571
0.7862
1%



galactinol-dihydrate-



turanose-kojibiose-D-



leucrose-lactulose-



sophorose-sucrose-beta-D-



lactose-D-trehalose-D-



cellobiose-D-Maltose-



palatinose-melibiose-alpha-



D-lactose


10782
Metabolite - 2486
35
0.427
0.6338
−15%


10785
Metabolite - 2506
35
0.1333
0.4318
−41%


10787
Metabolite - 2507
35
0.354
0.6113
−25%


10825
Metabolite - 2546
35
0.4672
0.6556
−13%


11053
Metabolite - 2567
35
0.7367
0.7434
−3%


11111
Metabolite - 2592
35
0.1638
0.4579
−62%


11219
Metabolite - 2686
35
0.7815
0.7448
−2%


11222
Metabolite - 2688
35
0.6332
0.73
−7%


11323
Metabolite - 2711
35
0.0047
0.0866
−21%


11438
phosphate
50
0.7922
0.7448
−1%


11499
Metabolite - 2753
35
0.3071
0.5847
−11%


11777
glycine
50
0.355
0.6113
−9%


11813
Metabolite - 2809
35
0.5982
0.7257
−10%


12035
nonanate
50
0.6366
0.73
2%


12109
Metabolite - 2853
35
0.0251
0.2202
−34%


12298
Metabolite - 2867
35
0.9249
0.7787
−4%


12478
Metabolite - 2898
35
0.4273
0.6338
30%


12532
Metabolite - 2914
50
0.8816
0.7596
0%


12533
Metabolite - 2915
50
0.1622
0.4579
14%


12543
2-hydroxy-butanoic acid
50
0.0286
0.2334
−29%


12562
Metabolite - 2955
50
0.5565
0.7129
−2%


12593
Metabolite - 2973
50
0.8623
0.7585
1%


12594
Metabolite - 2974
50
0.1248
0.4179
11%


12601
Metabolite - 2978
50
0.1299
0.4252
19%


12625
Metabolite - 3002
50
0.0819
0.355
−20%


12626
Metabolite - 3003
50
0.4436
0.6491
9%


12627
Metabolite - 3004
50
0.6919
0.7368
5%


12639
Metabolite - 3012
50
0.8549
0.7585
2%


12641
meso-erythritol
50
0.163
0.4579
−9%


12644
Metabolite - 3016
50
0.6845
0.7368
−3%


12645
Metabolite - 3017
50
0.7813
0.7448
−3%


12647
Metabolite - 3019
50
0.6788
0.7368
4%


12648
Metabolite - 3020
50
0.9322
0.7826
1%


12650
Metabolite - 3022
50
0.6859
0.7368
5%


12656
Metabolite - 3025
50
0.9228
0.7787
1%


12658
Metabolite - 3026
50
0.7257
0.7423
3%


12663
Metabolite - 3030
50
0.114
0.4081
12%


12666
Metabolite - 3033
50
0.0152
0.154
15%


12673
Metabolite - 3040
50
0.2695
0.5593
15%


12682
Metabolite - 3044
35
0.1443
0.4503
−18%


12719
Metabolite - 3055
35
0.5731
0.7241
15%


12720
Metabolite - 3056
35
0.9358
0.7834
1%


12726
Metabolite - 3058
50
0.6191
0.7298
9%


12739
1-5-anhydro-D-glucitol
50
0.7986
0.7448
−4%


12751
Metabolite - 3073
50
0.1953
0.4717
22%


12753
Metabolite - 3074
50
0.3904
0.6321
−22%


12754
Metabolite - 3075
50
0.2559
0.5505
15%


12756
Metabolite - 3077
50
0.5804
0.7241
5%


12757
Metabolite - 3078
50
0.2799
0.5648
11%


12761
Metabolite - 3081
50
0.8489
0.7585
1%


12765
inositol
50
0.5387
0.6992
−7%


12768
Metabolite - 3088
50
0.0017
0.0613
63%


12769
Metabolite - 3089
50
0.0293
0.2334
−26%


12771
Metabolite - 3091
50
0.4809
0.6576
22%


12773
Metabolite - 3093
50
0.4029
0.6338
−13%


12774
Metabolite - 3094
50
0.4972
0.666
−7%


12777
Metabolite - 3097
50
0.3855
0.6303
−14%


12780
Metabolite - 3098
50
0.2867
0.569
17%


12781
Metabolite - 3099
50
0.1762
0.4679
−19%


12784
Metabolite - 3102
50
0.3989
0.6338
−6%


12790
Metabolite - 3108
50
0.8644
0.7585
−1%


12876
Metabolite - 3125
35
0.7646
0.7448
−2%


12912
Metabolite - 3129
35
0.4822
0.6576
−8%


12924
Metabolite - 3131
35
0.3961
0.6338
23%


12931
DL-hexanoyl-carnitine
35
0.487
0.6583
−6%


12960
Metabolite - 3134
35
0.6922
0.7368
−11%


12969
Metabolite - 3135
35
0.9108
0.7713
−3%


13018
Metabolite - 3138
35
0.7404
0.7437
−4%


13038
Metabolite - 3143
35
0.1276
0.4226
−18%


13065
Metabolite - 3146
35
0.0976
0.3887
−35%


13104
Metabolite - 3160
35
0.6297
0.73
−6%


13142
Metabolite - 3165
35
0.7536
0.7448
−2%


13146
Metabolite - 3166
35
0.7532
0.7448
−7%


13148
Metabolite - 3167
35
0.217
0.5028
−16%


13179
possible-Metabolite - 3176-
35
0.1906
0.4682
22%



possible-creatine


13208
Metabolite - 3181
35
0.7725
0.7448
3%


13211
Metabolite - 3182
35
0.6544
0.7332
11%


13214
Metabolite - 3183-possible-
35
0.8943
0.766
−1%



gamma-L-glutamyl-L-



phenylalanine


13217
Metabolite - 3184
35
0.8706
0.7585
−2%


13249
Metabolite - 3215
35
0.4668
0.6556
−9%


13251
Metabolite - 3216
35
0.7987
0.7448
−4%


13257
Metabolite - 3218
35
0.5009
0.6678
−8%


13342
Metabolite - 3243
35
0.6378
0.73
−9%


13448
Metabolite - 3303
35
0.2433
0.5351
−9%


13459
Metabolite - 3305
35
0.0084
0.1083
−50%


13484
Metabolite - 3309
35
0.8307
0.7585
−4%


13505
Metabolite - 3313
35
0.3577
0.6113
−20%


13509
Metabolite - 3314
35
0.3672
0.6113
−12%


13534
Metabolite - 3320-possible-
35
0.4843
0.6576
−28%



pimpinellin-or-



tetrahydroxybenzophenone


13545
Metabolite - 3322
35
0
0.0014
−47%


13589
Metabolite - 3327
35
0.0057
0.0915
−50%


13775
Metabolite - 3370
35
0.3669
0.6113
−8%


13803
Metabolite - 3377
35
0.006
0.0915
−57%


13904
Metabolite - 3402
35
0.0721
0.3428
−26%


14027
Metabolite - 3426
35
0.7318
0.7434
1%


14084
Metabolite - 3436
35
0.6058
0.7257
−10%


14117
Metabolite - 3441
35
0.7013
0.7368
5%


14239
Metabolite - 3474
35
0.0599
0.3144
31%


14249
Metabolite - 3476
35
0.7249
0.7423
9%


14368
Metabolite - 3489
35
0.3626
0.6113
−20%


14439
Metabolite - 3498
35
0.5688
0.7241
6%


14495
Metabolite - 3534
35
0.0262
0.2202
−32%


14595
Metabolite - 3576
35
0.2107
0.4945
26%


14608
Metabolite - 3578
35
0.6691
0.7368
9%


14639
Metabolite - 3603
35
0.1163
0.4081
18%


14640
Metabolite - 3604
35
0.5838
0.7241
−13%


14672
Metabolite - 3615
35
0.6102
0.728
−10%


14715
Metabolite - 3653-possible-
35
0.473
0.6556
28%



stachydrine-


14766
Metabolite - 3670
35
0.147
0.4503
−13%


14785
isobar-
35
0.3213
0.5918
−25%



glycochenodeoxycholic



acid-glycodeoxycholic acid


14787
Metabolite - 3698
35
0.7067
0.7385
8%


14837
Metabolite - 3707
35
0.1711
0.4624
76%


14961
Metabolite - 3752
35
0.639
0.73
−25%


15000
Metabolite - 3758
35
0.1668
0.4593
−19%


15017
Metabolite - 3761
35
0.8791
0.7596
3%


15032
Metabolite - 3765
35
0.0335
0.2531
−38%


15063
Metabolite - 3772
35
0.1466
0.4503
−11%


15113
Metabolite - 3783
35
0.4353
0.6413
12%


15122
glycerol
50
0.056
0.3133
−13%


15128
DL-homocysteine
35
0.728
0.7423
3%


15129
D-alanyl-D-alanine
35
0.0754
0.3472
−21%


15211
Metabolite - 3807
35
0.8721
0.7585
−1%


15220
Metabolite - 3813
35
0.1744
0.4672
−20%


15227
Metabolite - 3816
35
0.8542
0.7585
−3%


15251
Metabolite - 3830
35
0.0126
0.1407
−36%


15253
Metabolite - 3832-possible-
35
0.7773
0.7448
−8%



phenol-sulfate


15278
Metabolite - 3843
35
0.8645
0.7585
−1%


15319
DL-phenyllactic acid
35
0.0478
0.2816
−41%


15326
Metabolite - 3879
35
0.7977
0.7448
13%


15328
azelaic acid
35
0.2378
0.5309
−9%


15336
tartaric acid
35
0.0388
0.2538
−38%


15365
sn-Glycerol-3-phosphate
50
0.2692
0.5593
−8%


15389
Metabolite - 3900
35
0.0079
0.1061
−16%


15500
carnitine
35
0.344
0.6106
7%


15529
Metabolite - 3951
35
0.2451
0.5351
9%


15535
Metabolite - 3955
35
0.3382
0.6063
37%


15606
Metabolite - 3968
35
0.9659
0.7862
1%


15612
Metabolite - 3972
35
0.7724
0.7448
2%


15626
Metabolite - 3977
35
0.1527
0.4554
−10%


15677
3-methyl-L-histidine
35
0.5533
0.712
3%


15681
4-Guanidinobutanoic acid
35
0.3014
0.5825
15%


15683
4-methyl-2-oxopentanoate
50
0.0405
0.2538
−20%


15704
heptanedioic acid
35
0.1181
0.4081
51%


15744
N—N-dimethylarginine
35
0.1838
0.4682
−11%


15753
hippuric acid
35
0.3545
0.6113
−17%


15991
L-alpha-
35
0.4761
0.6556
−16%



glycerophosphorylcholine


16002
Metabolite - 3992-possible-
35
0.586
0.7241
4%



Cl-adduct-of-Formate-dimer


16016
Metabolite - 3994
35
0.9895
0.7893
0%


16071
Metabolite - 4020
50
0.3655
0.6113
−6%


16091
Metabolite - 4031-possible-
35
0.1019
0.4004
−11%



norlevorphenol-



isobutylphendienamide-



amprolium


16107
lysine
50
0.1647
0.4579
−14%


16137
Metabolite - 4078
35
0.7185
0.7423
−8%


16161
gamma-glutamyl-glutamic
35
0.5784
0.7241
−8%



acid


16186
Metabolite - 4096-possible-
35
0.9805
0.7893
1%



gamma-glu-gly-leu-


16226
Isobar-28-includes-L-
35
0.2869
0.569
11%



threonine-L-allothreonine-



L-homoserine-S-4-amino-2-



hydroxybutyric acid


16231
Isobar-20-includes-fumaric
35
0.7914
0.7448
−5%



acid-3-methyl-2-



oxobutanoate


16232
Isobar-17-includes-arginine-
35
0.01
0.1225
38%



N-alpha-acetyl-ornithine


16233
Isobar-13-includes-5-keto-
35
0.1191
0.4081
−21%



D-gluconic acid-2-keto-L-



gulonic acid-D-glucuronic



acid-D-galacturonic acid


16235
Isobar-19-includes-D-
35
0.6445
0.73
8%



saccharic acid-1-5-anhydro-



D-glucitol-2-deoxy-D-



galactose-2-deoxy-D-



glucose-L-fucose-L-



rhamnose


16237
Isobar-25-includes-L-
35
0.821
0.756
−5%



gulono-1-4-lactone-glucono-



gamma-lactone-


16241
Isobar-30-includes-
35
0.2512
0.5443
−15%



maltotetraose-stachyose


16243
L-kynurenine
35
0.6009
0.7257
−5%


16244
Isobar-21-includes-gamma-
35
0.1351
0.4326
36%



aminobutyryl-L-histidine-L-



anserine


16246
Isobar-18-includes-D-
35
0.9657
0.7862
−1%



fructose-1-phosphate-beta-



D-fructose-6-phosphate


16279
Isobar-36-includes-D-
35
0.0397
0.2538
−26%



sorbitol-6-phosphate-



mannitol-1-phosphate


16290
Metabolite - 4133
50
0.1945
0.4717
16%


16308
Metabolite - 4147
50
0.1066
0.4081
−21%


16330
Metabolite - 4163
35
0.866
0.7585
−3%


16337
Metabolite - 4167
35
0.4046
0.6338
−14%


16462
Metabolite - 4234
35
0.7831
0.7448
−4%


16471
Metabolite - 4238
35
0.7117
0.741
−8%


16508
Metabolite - 4272
50
0.939
0.7839
−1%


16621
Metabolite - 4355
50
0.9609
0.7862
−1%


16653
Metabolite - 4361
50
0.8571
0.7585
−3%


16666
Metabolite - 4365
50
0.6891
0.7368
7%


16824
iminodiacetic acid
50
0.0261
0.2202
−23%


16829
Metabolite - 4503
50
0.839
0.7585
−7%


16848
Metabolite - 4511
50
0.0959
0.3887
−23%


16952
Metabolite - 4593
50
0.7253
0.7423
−2%


17028
Metabolite - 4611
50
0.7939
0.7448
−2%


17328
Metabolite - 4768
50
0.414
0.6338
−17%


17330
Metabolite - 4769
50
0.8061
0.7493
3%


17359
Metabolite - 4791
50
0.9964
0.7893
0%


17388
Metabolite - 4795
50
0.6053
0.7257
10%


17614
Metabolite - 4966
50
0.866
0.7585
2%


17627
Metabolite - 4986
50
0.4496
0.6495
−13%


18118
Metabolite - 5346
50
0.2656
0.559
−11%


18146
Metabolite - 5366
50
0.0574
0.3133
−23%


18232
Metabolite - 5403
50
0.6472
0.73
4%


18316
Metabolite - 5437
50
0.0382
0.2538
−38%


18335
D-quinic acid
50
0.0437
0.2628
−48%


18349
DL-indole-3-lactic acid
50
0.0021
0.0633
−22%


18868
Metabolite - 5847
50
0.3783
0.6227
−18%


18926
Metabolite - 5906
50
0.4724
0.6556
−29%


18929
Metabolite - 5907
50
0.5093
0.673
−6%









Example 4
Distinguish Lower Grade from Higher Grade, Urine
Biomarkers were discovered by (1) analyzing urine samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
The urine samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer, 43 individuals with lower grade prostate cancer (i.e. Gleason Score major=3) and 15 individuals with aggressive, high grade prostate cancer (i.e. Gleason Score major=4+). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Lower Grade Prostate cancer).
Biomarkers:
As listed below in Table 9, biomarkers were discovered that were differentially present between urine samples from subjects with lower grade prostate cancer and urine samples from Control subjects with negative prostate biopsies (i.e. not diagnosed with prostate cancer). Table 10 lists biomarkers that were discovered that were differentially present between urine samples from subjects with metastatic/high grade prostate cancer and urine samples from Control subjects with biopsy negative prostates (i.e. not diagnosed with prostate cancer). Table 11 lists biomarkers that were discovered that were differentially present between urine samples from subjects with metastatic/high grade prostate cancer and urine from subjects with lower grade prostate cancer.
Tables 9-11 include, for each listed biomarker, the p-value and q-value determined in the statistical analysis of the data concerning the biomarkers and an indication of the percentage difference in the lower grade prostate cancer mean level as compared to the control mean level (Table 9), the metastatic/high grade prostate cancer mean level as compared to the control mean level (Table 10), and the metastatic/high grade prostate cancer mean level as compared to the lower grade prostate cancer mean level (Table 11). The term “Isobar” as used in the tables indicates the compounds that could not be distinguished from each other on the analytical platform used in the analysis (i.e., the compounds in an isobar elute at nearly the same time and have similar (and sometimes exactly the same) quant ions, and thus cannot be distinguished). Library indicates the chemical library that was used to identify the compounds. The number 50 refers to the GC library and the number 35 refers to the LC library.
Biomarkers were discovered by (1) analyzing urine samples from different groups of human subjects to determine the levels of metabolites in the samples and then (2) statistically analyzing the results to determine those metabolites that were differentially present in the two groups.
The urine samples used for the analysis were from 53 control individuals with negative biopsies for prostate cancer, 43 individuals with lower grade prostate cancer (i.e. Gleason Score major=3) and 15 individuals with aggressive, high grade prostate cancer (i.e. Gleason Score major=4+). After the levels of metabolites were determined, the data was analyzed using univariate T-tests (i.e., Welch's T-test).
T-tests were used to determine differences in the mean levels of metabolites between two populations (i.e., Lower Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Control, Metastatic/High Grade Prostate cancer vs. Lower Grade Prostate cancer).







TABLE 9







Urine Metabolite Biomarkers to distinguish Non-cancer vs. Lower


Grade PCA

















% Change


COMP_ID
COMPOUND
LIB_ID
p-value
q-value
in PCA















53
glutamine
50
0.796
0.9846
5%


54
tryptophan
35
0.1502
0.9846
−15%


57
glutamic acid
50
0.855
0.9846
−3%


59
histidine
50
0.4545
0.9846
17%


60
leucine
50
0.7145
0.9846
8%


64
phenylalanine
35
0.6419
0.9846
−6%


418
guanine
50
0.9595
0.9875
1%


512
asparagine
50
0.4606
0.9846
−9%


513
creatinine
35
0.1826
0.9846
−10%


521
homogentisate
50
0.8571
0.9846
−5%


527
lactate
50
0.3716
0.9846
−9%


528
alpha-keto-glutarate
35
0.1009
0.9846
35%


531
3-hydroxy-3-
50
0.9687
0.9875
0%



methylglutarate


541
4-hydroxyphenylacetate
50
0.4362
0.9846
25%


542
3-hydroxybutanoic acid
50
0.6851
0.9846
27%


554
adenine
50
0.2417
0.9846
23%


555
adenosine
35
0.9098
0.9875
2%


563
alpha-L-sorbopyranose
50
0.9777
0.9875
−1%


569
caffeine
35
0.4377
0.9846
21%


575
arabinose
50
0.5366
0.9846
10%


577
fructose
50
0.4858
0.9846
31%


581
glucose
50
0.3339
0.9846
−77%


587
gluconic acid
50
0.5172
0.9846
14%


594
niacinamide
35
0.8901
0.9875
1%


597
phosphoenolpyruvate
35
0.4537
0.9846
−20%


605
uracil
50
0.4138
0.9846
15%


607
urocanic acid
35
0.2858
0.9846
39%


608
vitamin-B6
35
0.1525
0.9846
112%


1101
3-methoxy-4-
50
0.9705
0.9875
1%



hydroxyphenylacetate


1107
allantoin
50
0.6965
0.9846
6%


1125
isoleucine
50
0.4588
0.9846
−12%


1126
alanine
50
0.9256
0.9875
1%


1284
threonine
50
0.7919
0.9846
5%


1299
tyrosine
50
0.8374
0.9846
4%


1302
methionine
35
0.6757
0.9846
−6%


1303
malic acid
35
0.81
0.9846
6%


1366
trans-4-hydroxyproline
50
0.2618
0.9846
22%


1413
3-hydroxyphenylacetate
35
0.8047
0.9846
−4%


1417
kynurenic acid
50
0.9471
0.9875
−1%


1418
5-6-Dihydrothymine
35
0.9664
0.9875
−1%


1419
5-s-methyl-5-thioadenosine
35
0.2486
0.9846
−15%


1431
(p-Hydroxyphenyl)lactic
50
0.1211
0.9846
32%



acid


1432
alphahydroxybenzeneacetic
35
0.8358
0.9846
−2%



acid


1437
succinate
50
0.0633
0.9846
42%


1444
DL-pipecolic acid
35
0.9345
0.9875
−4%


1480
guanidineacetic acid
35
0.0371
0.9846
42%


1493
ornithine
50
0.2975
0.9846
54%


1494
5-oxoproline
50
0.4228
0.9846
14%


1498
N-6-trimethyl-l-lysine
35
0.2734
0.9846
18%


1505
orotic acid
50
0.2172
0.9846
26%


1508
pantothenic acid
35
0.9729
0.9875
−1%


1519
sucrose
50
0.3449
0.9846
95%


1557
3-methylglutaric acid
35
0.8338
0.9846
3%


1558
4-acetamidobutyric acid
35
0.3994
0.9846
−13%


1559
5-6-dihydrouracil
50
0.2764
0.9846
14%


1560
L-methyldopa
35
0.3931
0.9846
19%


1564
citric acid
50
0.4898
0.9846
13%


1566
3-amino-isobutyrate
50
0.3393
0.9846
41%


1567
4-hydroxy-3-
50
0.8926
0.9875
−3%



methoxymandelate


1568
4-hydroxymandelate
50
0.6452
0.9846
11%


1569
DL-beta-
35
0.4562
0.9846
16%



hydroxyphenylethylamine


1574
histamine
35
0.892
0.9875
−3%


1580
noradrenaline
50
0.6485
0.9846
11%


1585
N-acetyl-L-alanine
35
0.5936
0.9846
−8%


1587
N-acetyl-L-leucine
35
0.7574
0.9846
5%


1591
N-acetyl-L-valine
35
0.2762
0.9846
34%


1592
N-acetylneuraminic acid
50
0.9603
0.9875
−1%


1598
N-tigloylglycine
35
0.434
0.9846
13%


1604
uric acid
35
0.8166
0.9846
1%


1640
ascorbic acid
50
0.5353
0.9846
113%


1648
serine
50
0.448
0.9846
10%


1649
valine
50
0.8355
0.9846
4%


1708
7-8-dihydrofolic acid
35
0.3057
0.9846
10%


1778
gamma-glu-cys
35
0.9805
0.9875
−1%


1827
riboflavine
35
0.3791
0.9846
29%


1860
3-nitro-L-tyrosine
35
0.3596
0.9846
26%


1868
cysteine
50
0.3622
0.9846
69%


1898
proline
50
0.806
0.9846
−5%


1899
quinolinic acid
50
0.8475
0.9846
3%


2078
pyrophosphate
50
0.3881
0.9846
44%


2092
catechol
35
0.9299
0.9875
3%


2132
citrulline
50
0.1077
0.9846
29%


2183
thymidine
35
0.6528
0.9846
−7%


2245
Metabolite - 294
35
0.1857
0.9846
32%


2342
serotonin
35
0.631
0.9846
6%


2734
gamma-L-glutamyl-L-
35
0.1668
0.9846
−24%



tyrosine


2829
N-formyl-L-methionine
35
0.3164
0.9846
19%


2831
adenosine-3-5-cyclic-
35
0.4814
0.9846
−8%



monophosphate


3127
hypoxanthine
35
0.8698
0.9875
3%


3138
pyridoxamine-phosphate
35
0.3482
0.9846
−9%


3147
xanthine
35
0.3736
0.9846
10%


3155
3-ureidopropionic acid
35
0.3809
0.9846
17%


4966
xylitol
50
0.3043
0.9846
38%


5493
Metabolite - 1059
35
0.7607
0.9846
4%


5495
Metabolite - 1060
35
0.0016
0.6911
−17%


5514
Metabolite - 1081
35
0.904
0.9875
0%


5538
Metabolite - 1101
35
0.5358
0.9846
−21%


5664
Metabolite - 1101
35
0.506
0.9846
25%


5687
Metabolite - 1110
35
0.7134
0.9846
−6%


5697
acetylcarnitine-
35
0.6634
0.9846
12%


5702
Metabolite - 1114
35
0.4207
0.9846
−23%


5711
2-hydroxybutyric acid
35
0.7116
0.9846
7%


5719
Metabolite - 1122
35
0.5481
0.9846
11%


5727
Metabolite - 1126
35
0.541
0.9846
10%


5797
Metabolite - 1186
35
0.3318
0.9846
−14%


6137
Metabolite - 1212
35
0.2597
0.9846
−50%


6147
Metabolite - 1216
35
0.5806
0.9846
4%


6238
normetanephrine
50
0.8045
0.9846
−3%


6253
Metabolite - 1283
35
0.0674
0.9846
−25%


6278
Metabolite - 1289
35
0.7974
0.9846
4%


6329
urea
50
0.903
0.9875
2%


6362
Metabolite - 1323-possible-
35
0.4176
0.9846
18%



p-cresol-sulfate


6398
Metabolite - 1335
35
0.4128
0.9846
12%


6405
Metabolite - 1338
35
0.741
0.9846
−6%


6413
Metabolite - 1342-possible-
35
0.4637
0.9846
10%



phenylacetylglutamine-or-



formyl-N-acetyl-5-



methoxykynurenamine


6421
Metabolite - 1345
35
0.5336
0.9846
20%


6437
Metabolite - 1349-possible-
35
0.5691
0.9846
10%



N-acetyl-8-O-methyl-



Neuraminic acid


6443
Metabolite - 1351
35
0.3894
0.9846
23%


6477
Metabolite - 1364
35
0.3757
0.9846
167%


6486
Metabolite - 1368
35
0.5104
0.9846
−22%


6493
salicyluric acid
35
0.2953
0.9846
888%


6528
Metabolite - 1383-possible-
35
0.2172
0.9846
287%



salicyluric-glucuronide


6760
Metabolite - 1455
35
0.0407
0.9846
−22%


6764
Metabolite - 1459
35
0.1583
0.9846
36%


6777
Metabolite - 1463
35
0.172
0.9846
161%


6787
Metabolite - 1465
35
0.848
0.9846
−3%


6847
Metabolite - 1496
35
0.2291
0.9846
24%


6852
Metabolite - 1498
35
0.6978
0.9846
13%


6987
Metabolite - 1573
35
0.1323
0.9846
18%


7132
Metabolite - 1667
35
0.3324
0.9846
256%


7175
Metabolite - 1655
35
0.3706
0.9846
14%


7177
Metabolite - 1656
35
0.0404
0.9846
68%


7272
Metabolite - 1679
35
0.4554
0.9846
−10%


7286
Metabolite - 1682
35
0.363
0.9846
15%


7359
n-acetyl-L-aspartic acid
35
0.7265
0.9846
−6%


7639
oxalic acid
35
0.842
0.9846
2%


7650
Metabolite - 1834
35
0.6964
0.9846
−16%


7660
Metabolite - 1839
35
0.9696
0.9875
−1%


7672
Metabolite - 1843
35
0.5216
0.9846
−6%


7933
Metabolite - 1911
35
0.219
0.9846
41%


8176
Metabolite - 1974
35
0.4332
0.9846
20%


8196
Metabolite - 1979-Cl-
35
0.0901
0.9846
96%



adduct-of-isobar-19


8210
Metabolite - 1981
35
0.7764
0.9846
5%


8336
Metabolite - 2005
35
0.3343
0.9846
23%


8644
Metabolite - 2051
35
0.0878
0.9846
18%


8677
Metabolite - 2056
35
0.3734
0.9846
−12%


9007
Metabolite - 2108
35
0.2858
0.9846
−44%


9038
Metabolite - 2118
35
0.5665
0.9846
−7%


9113
Metabolite - 2133
35
0.1426
0.9846
−18%


9165
Metabolite - 2150
35
0.9275
0.9875
1%


9333
Metabolite - 2174
35
0.4734
0.9846
13%


9334
Metabolite - 2175
35
0.8327
0.9846
13%


9458
Metabolite - 2181
35
0.8365
0.9846
−3%


10058
Metabolite - 2242
35
0.3634
0.9846
427%


10087
Metabolite - 2249
35
0.3102
0.9846
−22%


10122
Metabolite - 2254
35
0.4777
0.9846
−40%


10136
Metabolite - 2034
35
0.8375
0.9846
−5%


10156
Metabolite - 2259
35
0.836
0.9846
−7%


10240
4-acetominophen-sulfate
35
0.2026
0.9846
34%


10245
Metabolite - 2269-
35
0.8222
0.9846
−2%


10247
Metabolite - 2270
35
0.6261
0.9846
15%


10252
Metabolite - 2271
35
0.2147
0.9846
30%


10286
Metabolite - 2272
35
0.4099
0.9846
−34%


10309
Metabolite - 2277
35
0.3674
0.9846
−12%


10347
Metabolite - 2285
35
0.8582
0.9846
4%


10407
Metabolite - 2059
35
0.663
0.9846
−6%


10424
Metabolite - 2292
35
0.1432
0.9846
30%


10433
Metabolite - 2293-possible-
35
0.3141
0.9846
1403%



O-desmethylvenlafaxine-



glucuronide


10490
Metabolite - 2319
35
0.83
0.9846
−4%


10526
Metabolite - 2323
35
0.8463
0.9846
4%


10544
Metabolite - 2329
35
0.9805
0.9875
1%


10555
Metabolite - 2348
35
0.2902
0.9846
65%


10570
Metabolite - 2366
35
0.1258
0.9846
−37%


10629
Metabolite - 2386
35
0.7455
0.9846
−4%


10644
Metabolite - 2387
35
0.3475
0.9846
−24%


10667
Metabolite - 2389
35
0.2017
0.9846
22%


10672
Metabolite - 2390
35
0.9346
0.9875
1%


10737
Isobar-1-includes-
35
0.4849
0.9846
−26%



mannose-fructose-glucose-



galactose-alpha-L-



sorbopyranose-Inositol-D-



allose-D--altrose-D-



psicone


10741
Isobar-2-includes-2-
35
0.356
0.9846
−61%



aminoisobutyric acid-3-



amino-isobutyrate-2-



amino-butyrate-4-



aminobutanoic acid-



dimethylglycine-choline-


10743
Isobar-4-includes-Gluconic
35
0.986
0.9883
0%



acid-DL-arabinose-D-



ribose-L-xylose-DL-



lyxose-D-xylulose


10746
Isobar-6-includes-valine-
35
0.8873
0.9875
4%



betaine


10785
Metabolite - 2506
35
0.6703
0.9846
7%


10825
Metabolite - 2546
35
0.3625
0.9846
13%


10872
Metabolite - 2550
35
0.5812
0.9846
−11%


10906
Metabolite - 2557-possible-
35
0.0411
0.9846
64%



Pantoprazole-metabolite


11053
Metabolite - 2567
35
0.7296
0.9846
5%


11085
Metabolite - 2588
35
0.2272
0.9846
25%


11110
Metabolite - 2591
35
0.4451
0.9846
17%


11173
Metabolite - 2607
35
0.2724
0.9846
42%


11219
Metabolite - 2686
35
0.4501
0.9846
13%


11264
Metabolite - 2698
35
0.6617
0.9846
27%


11271
Metabolite - 2700
35
0.1367
0.9846
48%


11292
Metabolite - 2703
35
0.6289
0.9846
−6%


11299
Metabolite - 2706
35
0.2913
0.9846
−22%


11390
Metabolite - 2726
35
0.3521
0.9846
−14%


11411
Metabolite - 2746
35
0.2543
0.9846
−21%


11438
phosphate
50
0.5453
0.9846
11%


11484
Metabolite - 2752
35
0.245
0.9846
18%


11661
Metabolite - 2781
35
0.7701
0.9846
−4%


11777
glycine
50
0.5674
0.9846
10%


11808
Metabolite - 2807
35
0.0487
0.9846
62%


11851
Metabolite - 2811
35
0.0085
0.9846
161%


12025
cis-aconitic acid
50
0.3727
0.9846
58%


12055
galactose
50
0.6975
0.9846
11%


12102
o-phosphoethanolamine
50
0.6267
0.9846
−13%


12104
Metabolite - 2852
35
0.5159
0.9846
29%


12109
Metabolite - 2853
35
0.9627
0.9875
1%


12129
beta-hydroxyisovaleric
50
0.8271
0.9846
4%



acid


12300
Metabolite - 2868
35
0.7519
0.9846
−16%


12358
(1′R,1′S)_biopterin
35
0.2306
0.9846
26%


12426
Metabolite - 2416
35
0.4534
0.9846
20%


12463
Metabolite - 2893-possible-
35
0.4566
0.9846
18%



demethylated-



Rosiglitazone


12474
Metabolite - 2897
35
0.2372
0.9846
−17%


12593
Metabolite - 2973
50
0.0377
0.9846
−25%


12641
meso-erythritol
50
0.9483
0.9875
−2%


12644
Metabolite - 3016
50
0.3011
0.9846
−8%


12648
Metabolite - 3020
50
0.8127
0.9846
5%


12666
Metabolite - 3033
50
0.8413
0.9846
3%


12711
Metabolite - 3053
35
0.5017
0.9846
24%


12720
Metabolite - 3056
35
0.5412
0.9846
8%


12765
inositol
50
0.4102
0.9846
−27%


12770
Metabolite - 3090
50
0.1121
0.9846
−11%


12771
Metabolite - 3091
50
0.2399
0.9846
−25%


12795
Metabolite - 3113
50
0.3928
0.9846
−14%


12856
Metabolite - 3123
35
0.4327
0.9846
17%


12902
Metabolite - 3127
35
0.765
0.9846
−4%


12904
Metabolite - 2457
35
0.0497
0.9846
66%


12924
Metabolite - 3131
35
0.7354
0.9846
−7%


12938
Metabolite - 2459
35
0.9267
0.9875
−1%


13018
Metabolite - 3138
35
0.9748
0.9875
0%


13136
Metabolite - 3163-possible-
35
0.9502
0.9875
1%



methylcytidine-



benserazide-Pyr-Gln-OH-



or-glycerophosphocholine-


13153
Metabolite - 3169
35
0.6836
0.9846
13%


13179
Metabolite - 3176
35
0.8382
0.9846
−13%


13214
Metabolite - 3183-possible-
35
0.6928
0.9846
8%



gamma-L-glutamyl-L-



phenylalanine


13217
Metabolite - 3184
35
0.3549
0.9846
10%


13249
Metabolite - 3215
35
0.8582
0.9846
3%


13251
Metabolite - 3216
35
0.3024
0.9846
−7%


13265
Metabolite - 3221
35
0.9343
0.9875
−2%


13297
Metabolite - 3231
35
0.9212
0.9875
−2%


13318
DL-indole-3-lactic acid
35
0.4237
0.9846
−19%


13356
Metabolite - 3246-possible-
35
0.5345
0.9846
−8%



Ala-GLy-glycyl-sarcosine-



or-ureido-butyric acid


13459
Metabolite - 3305
35
0.483
0.9846
16%


13484
Metabolite - 3309
35
0.8589
0.9846
3%


13493
Metabolite - 3311-
35
0.1888
0.9846
56%


13505
Metabolite - 3313
35
0.5469
0.9846
−13%


13534
Metabolite - 3320-possible-
35
0.6718
0.9846
13%



pimpinellin-or-



tetrahydroxybenzophenone


13545
Metabolite - 3322
35
0.393
0.9846
−14%


13589
Metabolite - 3327
35
0.2554
0.9846
26%


13594
Metabolite - 3329
35
0.9464
0.9875
−2%


13704
Metabolite - 3355
35
0.2556
0.9846
20%


13744
Metabolite - 3364
35
0.2659
0.9846
19%


13775
Metabolite - 3370
35
0.5874
0.9846
12%


13791
Metabolite - 3373
35
0.985
0.9883
0%


13803
Metabolite - 3377
35
0.5535
0.9846
−22%


13817
Metabolite - 3380
35
0.3112
0.9846
−11%


13820
beta-nicotinamide-
35
0.8355
0.9846
4%



mononucleotide


13847
Metabolite - 3387
35
0.7957
0.9846
4%


13904
Metabolite - 3402
35
0.3187
0.9846
71%


13968
Metabolite - 3409
35
0.3858
0.9846
18%


14036
Metabolite - 3427
35
0.7015
0.9846
8%


14066
Metabolite - 3433
35
0.7142
0.9846
−4%


14084
Metabolite - 3436
35
0.5508
0.9846
10%


14115
Metabolite - 3440
35
0.3104
0.9846
−64%


14125
Metabolite - 3443
35
0.5809
0.9846
11%


14170
Metabolite - 3457
35
0.6752
0.9846
12%


14220
Metabolite - 3470
35
0.8918
0.9875
4%


14249
Metabolite - 3476
35
0.0695
0.9846
82%


14368
Metabolite - 3489
35
0.3569
0.9846
−27%


14406
Metabolite - 3493
35
0.818
0.9846
3%


14453
Metabolite - 3507
35
0.5637
0.9846
14%


14471
Metabolite - 3516
35
0.2008
0.9846
34%


14506
Metabolite - 3543
35
0.5679
0.9846
−18%


14539
Metabolite - 3564
35
0.1262
0.9846
−38%


14595
Metabolite - 3576
35
0.4931
0.9846
9%


14640
Metabolite - 3604
35
0.1561
0.9846
20%


14641
Metabolite - 3605
35
0.1604
0.9846
44%


14731
Metabolite - 3659
35
0.4077
0.9846
18%


14732
Metabolite - 3660
35
0.2255
0.9846
31%


14733
Metabolite - 3661
35
0.7777
0.9846
−9%


14759
Metabolite - 3667
35
0.2647
0.9846
19%


14762
Metabolite - 3668
35
0.57
0.9846
−5%


14766
Metabolite - 3670
35
0.5103
0.9846
12%


14769
Metabolite - 3691
35
0.6776
0.9846
−8%


14808
Metabolite - 3701
35
0.0336
0.9846
−31%


14835
Metabolite - 3706
35
0.9101
0.9875
2%


14840
Metabolite - 3708
35
0.8511
0.9846
−6%


14907
Metabolite - 3734
35
0.3113
0.9846
16%


14983
Metabolite - 3754
35
0.9005
0.9875
−2%


14984
Metabolite - 3755
35
0.3521
0.9846
154%


15017
Metabolite - 3761
35
0.1689
0.9846
21%


15057
Metabolite - 3771
35
0.1457
0.9846
52%


15064
Metabolite - 3773
35
0.4225
0.9846
−10%


15096
N-acetyl-D-glucosamine
50
0.612
0.9846
10%


15121
Metabolite - 3786
35
0.3986
0.9846
20%


15124
porphobilinogen
35
0.8882
0.9875
2%


15125
(2-
35
0.1453
0.9846
14%



Aminoethyl)phosphonate


15128
DL-homocysteine
35
0.0781
0.9846
46%


15129
D-alanyl-D-alanine
35
0.9606
0.9875
1%


15130
diaminopimelic acid
35
0.4317
0.9846
−9%


15131
dethiobiotin
35
0.7544
0.9846
−6%


15187
Metabolite - 3800
35
0.7143
0.9846
−8%


15197
Metabolite - 3802
35
0.701
0.9846
8%


15201
Metabolite - 3803
35
0.3018
0.9846
16%


15202
Metabolite - 3804
35
0.213
0.9846
−22%


15203
Metabolite - 3805
35
0.9354
0.9875
−2%


15207
Metabolite - 3806
35
0.1744
0.9846
−33%


15211
Metabolite - 3807
35
0.8708
0.9875
2%


15220
Metabolite - 3813
35
0.3635
0.9846
17%


15228
Metabolite - 3817
35
0.5239
0.9846
−12%


15240
Metabolite - 3824
35
0.8028
0.9846
−7%


15249
Metabolite - 3828
35
0.8756
0.9875
3%


15251
Metabolite - 3830
35
0.0975
0.9846
39%


15253
Metabolite - 3832-possible-
35
0.2712
0.9846
−41%



phenol-sulfate


15258
Metabolite - 3834-Peptide
35
0.4949
0.9846
18%


15275
Metabolite - 3840
35
0.6594
0.9846
5%


15276
Metabolite - 3841
35
0.3623
0.9846
58%


15278
Metabolite - 3843
35
0.8581
0.9846
−4%


15284
Metabolite - 3847
35
0.9705
0.9875
0%


15294
Metabolite - 3855
35
0.8089
0.9846
5%


15312
Metabolite - 3873
35
0.609
0.9846
−8%


15315
Metabolite - 3876
35
0.379
0.9846
29%


15324
Metabolite - 3878
35
0.3307
0.9846
−18%


15326
Metabolite - 3879
35
0.9133
0.9875
−3%


15328
azelaic acid
35
0.1572
0.9846
−33%


15335
mannitol
50
0.123
0.9846
50%


15336
tartaric acid
35
0.2935
0.9846
−26%


15356
Metabolite - 3886
35
0.5807
0.9846
8%


15359
Metabolite - 3887
35
0.7867
0.9846
−5%


15365
sn-Glycerol-3-phosphate
50
0.8503
0.9846
−7%


15374
Metabolite - 3893
35
0.8837
0.9875
2%


15382
Metabolite - 3898
35
0.6325
0.9846
4%


15410
Metabolite - 3908
35
0.5194
0.9846
10%


15411
Metabolite - 3909
35
0.6385
0.9846
−23%


15418
Metabolite - 3911
35
0.4593
0.9846
8%


15496
agmatine
35
0.0364
0.9846
34%


15500
carnitine
35
0.7459
0.9846
10%


15529
Metabolite - 3951
35
0.9957
0.9957
0%


15532
Metabolite - 3952
35
0.4244
0.9846
−16%


15535
Metabolite - 3955
35
0.9603
0.9875
1%


15541
Metabolite - 3957
35
0.8287
0.9846
−3%


15599
Metabolite - 3963
35
0.3146
0.9846
24%


15610
Metabolite - 3970
35
0.4461
0.9846
17%


15620
Metabolite - 3973
35
0.3553
0.9846
44%


15626
Metabolite - 3977
35
0.1456
0.9846
−35%


15636
Metabolite - 3981
35
0.5962
0.9846
−16%


15641
Metabolite - 3986
35
0.6453
0.9846
−6%


15650
1-methyladenosine
35
0.8651
0.9875
−2%


15667
2-isopropylmalic acid
50
0.6338
0.9846
−24%


15676
3-methyl-2-oxovaleric acid
35
0.4947
0.9846
16%


15677
3-methyl-L-histidine
35
0.046
0.9846
−23%


15679
xanthurenic acid
50
0.5776
0.9846
14%


15681
4-Guanidinobutanoic acid
35
0.8135
0.9846
4%


15704
heptanedioic acid
35
0.7689
0.9846
−3%


15716
L-beta-imidazolelactic acid
50
0.5938
0.9846
18%


15730
suberic acid
35
0.2788
0.9846
−13%


15737
hydroxyacetic acid
50
0.5729
0.9846
−9%


15743
N-N-dimethylarginine
35
0.7457
0.9846
4%


15753
hippuric acid
35
0.4325
0.9846
14%


15778
benzoic acid
35
0.1887
0.9846
63%


15804
maltose
50
0.428
0.9846
64%


15835
L-xylose
50
0.7767
0.9846
10%


15948
S-adenosyl-l-homocysteine
35
0.6109
0.9846
−11%


15964
D-arabitol
50
0.9713
0.9875
1%


16002
Metabolite - 3992-possible-
35
0.1682
0.9846
16%



Cl-adduct-of-Formate-



dimer


16016
Metabolite - 3994
35
0.1703
0.9846
−24%


16034
Metabolite - 4002
50
0.1968
0.9846
30%


16071
Metabolite - 4020
50
0.6192
0.9846
8%


16082
Metabolite - 4027
50
0.7798
0.9846
5%


16107
lysine
50
0.2773
0.9846
145%


16175
Metabolite - 4092
35
0.4841
0.9846
−13%


16197
Metabolite - 4112
35
0.8282
0.9846
4%


16217
Metabolite - 4116
35
0.8574
0.9846
−6%


16230
Isobar-29-includes-R-S-
35
0.0326
0.9846
114%



hydroorotic acid-5-6-



dihydroorotic acid


16232
Isobar-17-includes-
35
0.7984
0.9846
5%



arginine-N-alpha-acetyl-



ornithine


16233
Isobar-13-includes-5-keto-
35
0.7037
0.9846
−8%



D-gluconic acid-2-keto-L-



gulonic acid-D-glucuronic



acid-D-galacturonic acid


16235
Isobar-19-includes-D-
35
0.1465
0.9846
66%



saccharic acid-1-5-



anhydro-D-glucitol-2-



deoxy-D-galactose-2-



deoxy-D-glucose-L-fucose-



L-rhamnose


16243
L-kynurenine
35
0.5787
0.9846
−8%


16276
Isobar-38-includes-N-
35
0.4495
0.9846
19%



acetyl-L-methionine-5-



hydroxy-1H-indole-3-



acetic acid


16278
Isobar-35-includes-D-
35
0.1346
0.9846
20%



arabinose-5-phosphate-D-



ribulose-5-phosphate-



alpha-D-ribose-5-



phosphate


16290
Metabolite - 4133
50
0.4411
0.9846
35%


16337
Metabolite - 4167
35
0.633
0.9846
12%


16338
Metabolite - 4168
35
0.6584
0.9846
20%


16457
Metabolite - 4233
35
0.4705
0.9846
21%


16462
Metabolite - 4234
35
0.1194
0.9846
57%


16496
Metabolite - 4251
50
0.1706
0.9846
−16%


16506
Metabolite - 4271
50
0.2282
0.9846
31%


16816
Metabolite - 4494
50
0.938
0.9875
−1%


16818
Metabolite - 4495
50
0.3478
0.9846
18%


16819
Metabolite - 4496
50
0.4825
0.9846
6%


16821
Metabolite - 4498
50
0.2269
0.9846
34%


16822
Metabolite - 4499
50
0.5555
0.9846
11%


16823
Metabolite - 4500
50
0.3974
0.9846
63%


16824
iminodiacetic acid
50
0.1445
0.9846
−23%


16827
Metabolite - 4502
50
0.6363
0.9846
−1%


16829
Metabolite - 4503
50
0.2869
0.9846
23%


16831
Metabolite - 4504
50
0.7348
0.9846
6%


16834
Metabolite - 4505
50
0.6099
0.9846
15%


16837
Metabolite - 4507
50
0.2767
0.9846
26%


16848
Metabolite - 4511
50
0.3715
0.9846
33%


16851
Metabolite - 4512
50
0.1504
0.9846
59%


16859
Metabolite - 4516
50
0.6517
0.9846
8%


16860
Metabolite - 4517
50
0.7046
0.9846
10%


16861
Metabolite - 4518
50
0.9422
0.9875
1%


16862
Metabolite - 4519
50
0.7079
0.9846
−11%


16863
Metabolite - 4520
50
0.9455
0.9875
−2%


16864
Metabolite - 4521
50
0.8773
0.9875
−5%


16865
Metabolite - 4522
50
0.6761
0.9846
7%


16866
Metabolite - 4523
50
0.7153
0.9846
6%


16867
Metabolite - 4524
50
0.2787
0.9846
−31%


16952
Metabolite - 4593
50
0.2049
0.9846
18%


16959
Metabolite - 4595
50
0.7468
0.9846
3%


17028
Metabolite - 4611
50
0.872
0.9875
3%


17050
Metabolite - 4618
50
0.2699
0.9846
72%


17064
Metabolite - 4624
50
0.3903
0.9846
13%


17072
Metabolite - 4628
50
0.2516
0.9846
81%


17074
Metabolite - 4629
50
0.6487
0.9846
9%


17080
Metabolite - 4632
50
0.8257
0.9846
7%


17083
Metabolite - 4634
50
0.7731
0.9846
6%


17084
Metabolite - 4635
50
0.3361
0.9846
134%


17085
Metabolite - 4636
50
0.5178
0.9846
18%


17086
Metabolite - 4637
50
0.834
0.9846
7%


17087
Metabolite - 4638
50
0.2699
0.9846
44%


17088
Metabolite - 4639
50
0.3228
0.9846
32%
















TABLE 10







Urine Metabolite Biomarkers to distinguish Non-cancer from Higher


Grade PCA.

















%







Change


COMP_ID
COMPOUND
LIB_ID
p-value
q-value
in PCA















53
glutamine
50
0.2634
0.2182
39%


54
tryptophan
35
0.1769
0.1876
25%


57
glutamic acid
50
0.3771
0.2666
18%


59
histidine
50
0.1191
0.1705
61%


60
leucine
50
0.0862
0.1546
58%


64
phenylalanine
35
0.0753
0.1546
33%


418
guanine
50
0.0722
0.1546
56%


512
asparagine
50
0.1886
0.1931
45%


513
creatinine
35
0.1327
0.1736
21%


521
homogentisate
50
0.1389
0.1744
59%


527
lactate
50
0.4598
0.2867
−11%


528
alpha-keto-glutarate
35
0.7074
0.3708
12%


531
3-hydroxy-3-
50
0.378
0.2666
24%



methylglutarate


541
4-hydroxyphenylacetate
50
0.2908
0.2279
32%


542
3-hydroxybutanoic acid
50
0.1308
0.1723
−48%


554
adenine
50
0.0464
0.1546
55%


555
adenosine
35
0.0068
0.1546
84%


563
alpha-L-sorbopyranose
50
0.2249
0.2026
92%


569
caffeine
35
0.0527
0.1546
−43%


575
arabinose
50
0.0227
0.1546
88%


577
fructose
50
0.4822
0.2929
41%


581
glucose
50
0.4136
0.2782
−65%


587
gluconic acid
50
0.0697
0.1546
86%


594
niacinamide
35
0.6385
0.3496
−8%


597
phosphoenolpyruvate
35
0.6788
0.3622
20%


605
uracil
50
0.0194
0.1546
55%


607
urocanic acid
35
0.0836
0.1546
54%


608
vitamin-B6
35
0.0887
0.1575
79%


1101
3-methoxy-4-
50
0.0139
0.1546
57%



hydroxyphenylacetate


1107
allantoin
50
0.0457
0.1546
83%


1125
isoleucine
50
0.3971
0.272
16%


1126
alanine
50
0.2068
0.1964
36%


1284
threonine
50
0.0516
0.1546
45%


1299
tyrosine
50
0.0503
0.1546
45%


1302
methionine
35
0.0169
0.1546
45%


1303
malic acid
35
0.5118
0.3041
18%


1366
trans-4-hydroxyproline
50
0.229
0.2026
32%


1413
3-hydroxyphenylacetate
35
0.671
0.36
12%


1417
kynurenic acid
50
0.172
0.1874
66%


1418
5-6-Dihydrothymine
35
0.0782
0.1546
44%


1419
5-s-methyl-5-
35
0.9786
0.4388
0%



thioadenosine


1431
(p-Hydroxyphenyl)lactic
50
0.2483
0.2111
87%



acid


1432
alphahydroxybenzeneacetic
35
0.7995
0.3952
4%



acid


1437
succinate
50
0.0769
0.1546
62%


1444
DL-pipecolic acid
35
0.728
0.3756
13%


1480
guanidineacetic acid
35
0.0049
0.1546
184%


1493
ornithine
50
0.062
0.1546
52%


1494
5-oxoproline
50
0.1124
0.1698
42%


1498
N-6-trimethyl-1-lysine
35
0.0433
0.1546
62%


1505
orotic acid
50
0.0559
0.1546
74%


1508
pantothenic acid
35
0.3273
0.2426
56%


1519
sucrose
50
0.102
0.1641
95%


1557
3-methylglutaric acid
35
0.6501
0.3538
−9%


1558
4-acetamidobutyric acid
35
0.1142
0.1698
39%


1559
5-6-dihydrouracil
50
0.0325
0.1546
44%


1560
L-methyldopa
35
0.2445
0.2093
36%


1564
citric acid
50
0.0304
0.1546
62%


1566
3-amino-isobutyrate
50
0.1884
0.1931
64%


1567
4-hydroxy-3-
50
0.0913
0.1595
48%



methoxymandelate


1568
4-hydroxymandelate
50
0.1129
0.1698
62%


1569
DL-beta-
35
0.1404
0.1744
36%



hydroxyphenylethylamine


1574
histamine
35
0.0267
0.1546
57%


1580
noradrenaline
50
0.1426
0.1744
67%


1585
N-acetyl-L-alanine
35
0.8018
0.3953
5%


1587
N-acetyl-L-leucine
35
0.1032
0.1641
49%


1591
N-acetyl-L-valine
35
0.0682
0.1546
101%


1592
N-acetylneuraminic acid
50
0.035
0.1546
46%


1598
N-tigloylglycine
35
0.0515
0.1546
46%


1604
uric acid
35
0.243
0.2093
6%


1640
ascorbic acid
50
0.3011
0.2324
228%


1648
serine
50
0.016
0.1546
60%


1649
valine
50
0.0849
0.1546
31%


1708
7-8-dihydrofolic acid
35
0.0656
0.1546
36%


1778
gamma-glu-cys
35
0.4751
0.2914
45%


1827
riboflavine
35
0.1656
0.1865
264%


1860
3-nitro-L-tyrosine
35
0.4409
0.2848
25%


1868
cysteine
50
0.1193
0.1705
108%


1898
proline
50
0.3203
0.2413
39%


1899
quinolinic acid
50
0.0925
0.1595
44%


2078
pyrophosphate
50
0.0839
0.1546
107%


2092
catechol
35
0.0165
0.1546
151%


2132
citrulline
50
0.0064
0.1546
73%


2183
thymidine
35
0.8414
0.4032
−4%


2245
Metabolite - 294
35
0.1285
0.1705
89%


2342
serotonin
35
0.0389
0.1546
41%


2734
gamma-L-glutamyl-L-
35
0.3139
0.2394
26%



tyrosine


2829
N-formyl-L-methionine
35
0.1969
0.195
46%


2831
adenosine-3-5-cyclic-
35
0.0306
0.1546
32%



monophosphate


3127
hypoxanthine
35
0.1978
0.195
56%


3138
pyridoxamine-phosphate
35
0.752
0.3841
−5%


3147
xanthine
35
0.148
0.1787
77%


3155
3-ureidopropionic acid
35
0.069
0.1546
96%


4966
xylitol
50
0.7869
0.3926
−5%


5493
Metabolite - 1059
35
0.9512
0.4306
1%


5495
Metabolite - 1060
35
0.1027
0.1641
−19%


5514
Metabolite - 1081
35
0.008
0.1546
11%


5538
Metabolite - 1101
35
0.6862
0.363
26%


5664
Metabolite - 1101
35
0.7561
0.3849
6%


5687
Metabolite - 1110
35
0.4575
0.2863
16%


5697
acetylcarnitine-
35
0.9057
0.4171
4%


5702
Metabolite - 1114
35
0.477
0.2917
27%


5711
2-hydroxybutyric acid
35
0.9468
0.4297
2%


5719
Metabolite - 1122
35
0.1964
0.195
24%


5727
Metabolite - 1126
35
0.7746
0.3891
8%


5797
Metabolite - 1186
35
0.6024
0.3354
12%


6137
Metabolite - 1212
35
0.479
0.2919
−32%


6147
Metabolite - 1216
35
0.7457
0.3827
−5%


6238
normetanephrine
50
0.2267
0.2026
13%


6253
Metabolite - 1283
35
0.9728
0.4373
1%


6278
Metabolite - 1289
35
0.1762
0.1876
17%


6329
urea
50
0.1643
0.1865
27%


6362
Metabolite - 1323-
35
0.0787
0.1546
84%



possible-p-cresol-sulfate


6398
Metabolite - 1335
35
0.1991
0.195
25%


6405
Metabolite - 1338
35
0.3289
0.2426
−21%


6413
Metabolite - 1342-
35
0.0596
0.1546
40%



possible-



phenylacetylglutamine-



or-formyl-N-acetyl-5-



methoxykynurenamine


6421
Metabolite - 1345
35
0.1218
0.1705
105%


6437
Metabolite - 1349-
35
0.0435
0.1546
54%



possible-N-acetyl-8-O-



methyl-Neuraminic acid


6443
Metabolite - 1351
35
0.5184
0.3061
26%


6477
Metabolite - 1364
35
0.8749
0.413
−6%


6486
Metabolite - 1368
35
0.7964
0.3952
13%


6493
salicyluric acid
35
0.3168
0.2401
243%


6528
Metabolite - 1383-
35
0.1243
0.1705
97%



possible-salicyluric-



glucuronide


6760
Metabolite - 1455
35
0.1951
0.195
23%


6764
Metabolite - 1459
35
0.386
0.2688
54%


6777
Metabolite - 1463
35
0.3817
0.2674
79%


6787
Metabolite - 1465
35
0.3552
0.2553
16%


6847
Metabolite - 1496
35
0.4314
0.2831
43%


6852
Metabolite - 1498
35
0.2973
0.2314
67%


6987
Metabolite - 1573
35
0.0136
0.1546
38%


7132
Metabolite - 1667
35
0.9013
0.4171
−3%


7175
Metabolite - 1655
35
0.0662
0.1546
103%


7177
Metabolite - 1656
35
0.0932
0.1595
106%


7272
Metabolite - 1679
35
0.2252
0.2026
28%


7286
Metabolite - 1682
35
0.4881
0.2937
19%


7359
n-acetyl-L-aspartic acid
35
0.0973
0.1641
56%


7639
oxalic acid
35
0.1037
0.1641
28%


7650
Metabolite - 1834
35
0.3481
0.2512
−34%


7660
Metabolite - 1839
35
0.9015
0.4171
−4%


7672
Metabolite - 1843
35
0.2013
0.1955
21%


7933
Metabolite - 1911
35
0.0604
0.1546
100%


8176
Metabolite - 1974
35
0.0348
0.1546
71%


8196
Metabolite - 1979-Cl-
35
0.0609
0.1546
77%



adduct-of-isobar-19


8210
Metabolite - 1981
35
0.7647
0.3861
6%


8336
Metabolite - 2005
35
0.6452
0.3522
10%


8644
Metabolite - 2051
35
0.041
0.1546
27%


8677
Metabolite - 2056
35
0.5849
0.3294
9%


9007
Metabolite - 2108
35
0.4471
0.2848
−34%


9038
Metabolite - 2118
35
0.3323
0.2426
20%


9113
Metabolite - 2133
35
0.6941
0.3651
8%


9165
Metabolite - 2150
35
0.3174
0.2401
30%


9333
Metabolite - 2174
35
0.2248
0.2026
29%


9334
Metabolite - 2175
35
0.2046
0.1961
95%


9458
Metabolite - 2181
35
0.0134
0.1546
52%


10058
Metabolite - 2242
35
0.0104
0.1546
−55%


10087
Metabolite - 2249
35
0.4419
0.2848
39%


10122
Metabolite - 2254
35
0.4675
0.2896
−41%


10136
Metabolite - 2034
35
0.4115
0.2778
35%


10156
Metabolite - 2259
35
0.3889
0.2693
71%


10240
4-acetominophen-sulfate
35
0.1068
0.1675
54%


10245
Metabolite - 2269-
35
0.8384
0.4028
3%


10247
Metabolite - 2270
35
0.2488
0.2111
−42%


10252
Metabolite - 2271
35
0.0323
0.1546
79%


10286
Metabolite - 2272
35
0.7248
0.375
19%


10309
Metabolite - 2277
35
0.0567
0.1546
39%


10347
Metabolite - 2285
35
0.0852
0.1546
50%


10407
Metabolite - 2059
35
0.4659
0.2896
14%


10424
Metabolite - 2292
35
0.3819
0.2674
−17%


10433
Metabolite - 2293-
35
0.1642
0.1865
35%



possible-O-



desmethylvenlafaxine-



glucuronide


10490
Metabolite - 2319
35
0.8212
0.3991
4%


10526
Metabolite - 2323
35
0.713
0.372
11%


10544
Metabolite - 2329
35
0.4846
0.2934
12%


10555
Metabolite - 2348
35
0.8929
0.4163
5%


10570
Metabolite - 2366
35
0.2076
0.1964
−29%


10629
Metabolite - 2386
35
0.4286
0.2831
14%


10644
Metabolite - 2387
35
0.8787
0.4132
6%


10667
Metabolite - 2389
35
0.7983
0.3952
−5%


10672
Metabolite - 2390
35
0.0662
0.1546
70%


10737
Isobar-1-includes-
35
0.4454
0.2848
−28%



mannose-fructose-



glucose-galactose-alpha-



L-sorbopyranose-Inositol-



D-allose-D--altrose-D-



psicone


10741
Isobar-2-includes-2-
35
0.3313
0.2426
−65%



aminoisobutyric acid-3-



amino-isobutyrate-2-



amino-butyrate-4-



aminobutanoic acid-



dimethylglycine-choline-


10743
Isobar-4-includes-
35
0.0302
0.1546
48%



Gluconic acid-DL-



arabinose-D-ribose-L-



xylose-DL-lyxose-D-



xylulose


10746
Isobar-6-includes-valine-
35
0.3058
0.2341
19%



betaine


10785
Metabolite - 2506
35
0.6343
0.3485
11%


10825
Metabolite - 2546
35
0.119
0.1705
29%


10872
Metabolite - 2550
35
0.1693
0.1865
77%


10906
Metabolite - 2557-
35
0.1732
0.1874
51%



possible-Pantoprazole-



metabolite


11053
Metabolite - 2567
35
0.0188
0.1546
49%


11085
Metabolite - 2588
35
0.2532
0.2129
105%


11110
Metabolite - 2591
35
0.2696
0.2198
−24%


11173
Metabolite - 2607
35
0.2777
0.2216
59%


11219
Metabolite - 2686
35
0.4301
0.2831
18%


11264
Metabolite - 2698
35
0.5771
0.3274
−27%


11271
Metabolite - 2700
35
0.116
0.1705
91%


11292
Metabolite - 2703
35
0.2307
0.2026
17%


11299
Metabolite - 2706
35
0.8211
0.3991
−6%


11390
Metabolite - 2726
35
0.5251
0.308
13%


11411
Metabolite - 2746
35
0.1037
0.1641
−29%


11438
phosphate
50
0.0685
0.1546
42%


11484
Metabolite - 2752
35
0.0063
0.1546
60%


11661
Metabolite - 2781
35
0.1145
0.1698
25%


11777
glycine
50
0.0284
0.1546
58%


11808
Metabolite - 2807
35
0.1406
0.1744
64%


11851
Metabolite - 2811
35
0.026
0.1546
235%


12025
cis-aconitic acid
50
0.1274
0.1705
76%


12055
galactose
50
0.7432
0.3824
14%


12102
o-phosphoethanolamine
50
0.7644
0.3861
8%


12104
Metabolite - 2852
35
0.1765
0.1876
285%


12109
Metabolite - 2853
35
0.6347
0.3485
15%


12129
beta-hydroxyisovaleric
50
0.066
0.1546
49%



acid


12300
Metabolite - 2868
35
0.4388
0.2848
76%


12358
(1′R,1′S)_biopterin
35
0.1576
0.1865
30%


12426
Metabolite - 2416
35
0.1652
0.1865
72%


12463
Metabolite - 2893-
35
0.4067
0.2755
27%



possible-demethylated-



Rosiglitazone


12474
Metabolite - 2897
35
0.8628
0.4093
−4%


12593
Metabolite - 2973
50
0.1595
0.1865
−22%


12641
meso-erythritol
50
0.3364
0.2437
28%


12644
Metabolite - 3016
50
0.72
0.3736
−4%


12648
Metabolite - 3020
50
0.0217
0.1546
69%


12666
Metabolite - 3033
50
0.0719
0.1546
51%


12711
Metabolite - 3053
35
0.788
0.3926
14%


12720
Metabolite - 3056
35
0.0489
0.1546
41%


12765
inositol
50
0.4194
0.2789
−27%


12770
Metabolite - 3090
50
0.3345
0.2432
12%


12771
Metabolite - 3091
50
0.3988
0.2721
37%


12795
Metabolite - 3113
50
0.5631
0.3223
−15%


12856
Metabolite - 3123
35
0.7525
0.3841
8%


12902
Metabolite - 3127
35
0.6832
0.363
10%


12904
Metabolite - 2457
35
0.169
0.1865
83%


12924
Metabolite - 3131
35
0.4335
0.2834
22%


12938
Metabolite - 2459
35
0.6893
0.3637
10%


13018
Metabolite - 3138
35
0.669
0.36
12%


13136
Metabolite - 3163-
35
0.2764
0.2216
19%



possible-methylcytidine-



benserazide-Pyr-Gln-OH-



or-



glycerophosphocholine-


13153
Metabolite - 3169
35
0.2308
0.2026
162%


13179
Metabolite - 3176
35
0.8221
0.3991
14%


13214
Metabolite - 3183-
35
0.0768
0.1546
57%



possible-gamma-L-



glutamyl-L-phenylalanine


13217
Metabolite - 3184
35
0.0416
0.1546
51%


13249
Metabolite - 3215
35
0.0164
0.1546
45%


13251
Metabolite - 3216
35
0.2086
0.1964
9%


13265
Metabolite - 3221
35
0.2654
0.2182
31%


13297
Metabolite - 3231
35
0.8602
0.4091
4%


13318
DL-indole-3-lactic acid
35
0.7643
0.3861
−9%


13356
Metabolite - 3246-
35
0.0822
0.1546
62%



possible-Ala-GLy-glycyl-



sarcosine-or-ureido-



butyric acid


13459
Metabolite - 3305
35
0.0755
0.1546
71%


13484
Metabolite - 3309
35
0.3911
0.2698
17%


13493
Metabolite - 3311-
35
0.837
0.4028
−6%


13505
Metabolite - 3313
35
0.9682
0.4363
1%


13534
Metabolite - 3320-
35
0.4164
0.2789
51%



possible-pimpinellin-or-



tetrahydroxybenzophenone


13545
Metabolite - 3322
35
0.1275
0.1705
63%


13589
Metabolite - 3327
35
0.085
0.1546
74%


13594
Metabolite - 3329
35
0.0641
0.1546
145%


13704
Metabolite - 3355
35
0.1883
0.1931
33%


13744
Metabolite - 3364
35
0.8656
0.4096
−3%


13775
Metabolite - 3370
35
0.0505
0.1546
51%


13791
Metabolite - 3373
35
0.3231
0.2424
1137%


13803
Metabolite - 3377
35
0.882
0.4132
7%


13817
Metabolite - 3380
35
0.1975
0.195
36%


13820
beta-nicotinamide-
35
0.0287
0.1546
51%



mononucleotide


13847
Metabolite - 3387
35
0.2135
0.2001
28%


13904
Metabolite - 3402
35
0.6861
0.363
6%


13968
Metabolite - 3409
35
0.5164
0.3059
22%


14036
Metabolite - 3427
35
0.0743
0.1546
72%


14066
Metabolite - 3433
35
0.5622
0.3223
7%


14084
Metabolite - 3436
35
0.5088
0.3032
13%


14115
Metabolite - 3440
35
0.2994
0.232
−66%


14125
Metabolite - 3443
35
0.0258
0.1546
−49%


14170
Metabolite - 3457
35
0.9959
0.4445
0%


14220
Metabolite - 3470
35
0.0581
0.1546
91%


14249
Metabolite - 3476
35
0.0267
0.1546
66%


14368
Metabolite - 3489
35
0.1102
0.1698
−48%


14406
Metabolite - 3493
35
0.3257
0.2426
21%


14453
Metabolite - 3507
35
0.774
0.3891
8%


14471
Metabolite - 3516
35
0.7774
0.3894
6%


14506
Metabolite - 3543
35
0.4448
0.2848
73%


14539
Metabolite - 3564
35
0.5935
0.3317
29%


14595
Metabolite - 3576
35
0.1252
0.1705
78%


14640
Metabolite - 3604
35
0.4348
0.2834
20%


14641
Metabolite - 3605
35
0.1679
0.1865
78%


14731
Metabolite - 3659
35
0.182
0.1904
34%


14732
Metabolite - 3660
35
0.3269
0.2426
64%


14733
Metabolite - 3661
35
0.5283
0.308
17%


14759
Metabolite - 3667
35
0.2604
0.217
24%


14762
Metabolite - 3668
35
0.473
0.2914
−11%


14766
Metabolite - 3670
35
0.6732
0.3602
8%


14769
Metabolite - 3691
35
0.0229
0.1546
116%


14808
Metabolite - 3701
35
0.716
0.3725
11%


14835
Metabolite - 3706
35
0.2566
0.2148
21%


14840
Metabolite - 3708
35
0.2166
0.2008
166%


14907
Metabolite - 3734
35
0.0383
0.1546
73%


14983
Metabolite - 3754
35
0.9142
0.4199
−3%


14984
Metabolite - 3755
35
0.9378
0.4275
1%


15017
Metabolite - 3761
35
0.029
0.1546
40%


15057
Metabolite - 3771
35
0.4518
0.2856
38%


15064
Metabolite - 3773
35
0.8169
0.3991
5%


15096
N-acetyl-D-glucosamine
50
0.016
0.1546
100%


15121
Metabolite - 3786
35
0.5899
0.3306
17%


15124
porphobilinogen
35
0.2695
0.2198
25%


15125
(2-
35
0.0023
0.1546
42%



Aminoethyl)phosphonate


15128
DL-homocysteine
35
0.0263
0.1546
76%


15129
D-alanyl-D-alanine
35
0.1999
0.195
28%


15130
diaminopimelic acid
35
0.1669
0.1865
36%


15131
dethiobiotin
35
0.4736
0.2914
64%


15187
Metabolite - 3800
35
0.1387
0.1744
68%


15197
Metabolite - 3802
35
0.2646
0.2182
50%


15201
Metabolite - 3803
35
0.049
0.1546
69%


15202
Metabolite - 3804
35
0.3305
0.2426
26%


15203
Metabolite - 3805
35
0.18
0.1894
29%


15207
Metabolite - 3806
35
0.5382
0.3128
31%


15211
Metabolite - 3807
35
0.0225
0.1546
33%


15220
Metabolite - 3813
35
0.083
0.1546
48%


15228
Metabolite - 3817
35
0.14
0.1744
43%


15240
Metabolite - 3824
35
0.9991
0.4448
1%


15249
Metabolite - 3828
35
0.1281
0.1705
48%


15251
Metabolite - 3830
35
0.1474
0.1787
67%


15253
Metabolite - 3832-
35
0.2771
0.2216
−40%



possible-phenol-sulfate


15258
Metabolite - 3834-Peptide
35
0.2916
0.2279
50%


15275
Metabolite - 3840
35
0.419
0.2789
17%


15276
Metabolite - 3841
35
0.2765
0.2216
39%


15278
Metabolite - 3843
35
0.2183
0.2008
42%


15284
Metabolite - 3847
35
0.9603
0.4337
2%


15294
Metabolite - 3855
35
0.9398
0.4275
2%


15312
Metabolite - 3873
35
0.2025
0.1956
30%


15315
Metabolite - 3876
35
0.8981
0.4171
7%


15324
Metabolite - 3878
35
0.4489
0.2848
−19%


15326
Metabolite - 3879
35
0.5546
0.3194
36%


15328
azelaic acid
35
0.6594
0.3573
−15%


15335
mannitol
50
0.1881
0.1931
65%


15336
tartaric acid
35
0.5703
0.3245
24%


15356
Metabolite - 3886
35
0.2185
0.2008
26%


15359
Metabolite - 3887
35
0.9902
0.443
0%


15365
sn-Glycerol-3-phosphate
50
0.6605
0.3573
14%


15374
Metabolite - 3893
35
0.4206
0.2789
18%


15382
Metabolite - 3898
35
0.1721
0.1874
19%


15410
Metabolite - 3908
35
0.0752
0.1546
65%


15411
Metabolite - 3909
35
0.4575
0.2863
−35%


15418
Metabolite - 3911
35
0.2886
0.2274
16%


15496
agmatine
35
0.5278
0.308
25%


15500
carnitine
35
0.3618
0.2584
−24%


15529
Metabolite - 3951
35
0.0523
0.1546
34%


15532
Metabolite - 3952
35
0.5521
0.319
25%


15535
Metabolite - 3955
35
0.0719
0.1546
72%


15541
Metabolite - 3957
35
0.8591
0.4091
3%


15599
Metabolite - 3963
35
0.4048
0.2752
114%


15610
Metabolite - 3970
35
0.0812
0.1546
45%


15620
Metabolite - 3973
35
0.1635
0.1865
179%


15626
Metabolite - 3977
35
0.8247
0.3993
7%


15636
Metabolite - 3981
35
0.6037
0.3354
25%


15641
Metabolite - 3986
35
0.9057
0.4171
2%


15650
1-methyladenosine
35
0.0502
0.1546
51%


15667
2-isopropylmalic acid
50
0.5859
0.3294
−27%


15676
3-methyl-2-oxovaleric
35
0.8809
0.4132
5%



acid


15677
3-methyl-L-histidine
35
0.3622
0.2584
16%


15679
xanthurenic acid
50
0.2292
0.2026
43%


15681
4-Guanidinobutanoic acid
35
0.1143
0.1698
38%


15704
heptanedioic acid
35
0.0573
0.1546
38%


15716
L-beta-imidazolelactic
50
0.2314
0.2026
55%



acid


15730
suberic acid
35
0.9187
0.421
−3%


15737
hydroxyacetic acid
50
0.2051
0.1961
26%


15743
N-N-dimethylarginine
35
0.1269
0.1705
30%


15753
hippuric acid
35
0.2825
0.2245
26%


15778
benzoic acid
35
0.8138
0.3991
6%


15804
maltose
50
0.8907
0.4163
−6%


15835
L-xylose
50
0.3032
0.233
61%


15948
S-adenosyl-l-
35
0.3769
0.2666
24%



homocysteine


15964
D-arabitol
50
0.0555
0.1546
53%


16002
Metabolite - 3992-
35
0.6621
0.3573
6%



possible-Cl-adduct-of-



Formate-dimer


16016
Metabolite - 3994
35
0.1773
0.1876
44%


16034
Metabolite - 4002
50
0.0999
0.1641
53%


16071
Metabolite - 4020
50
0.0376
0.1546
55%


16082
Metabolite - 4027
50
0.1234
0.1705
39%


16107
lysine
50
0.2204
0.2015
72%


16175
Metabolite - 4092
35
0.8448
0.4038
6%


16197
Metabolite - 4112
35
0.1002
0.1641
50%


16217
Metabolite - 4116
35
0.6325
0.3485
22%


16230
Isobar-29-includes-R—S-
35
0.0858
0.1546
404%



hydroorotic acid-5-6-



dihydroorotic acid


16232
Isobar-17-includes-
35
0.502
0.3001
−19%



arginine-N-alpha-acetyl-



ornithine


16233
Isobar-13-includes-5-
35
0.4534
0.2856
49%



keto-D-gluconic acid-2-



keto-L-gulonic acid-D-



glucuronic acid-D-



galacturonic acid


16235
Isobar-19-includes-D-
35
0.0455
0.1546
103%



saccharic acid-1-5-



anhydro-D-glucitol-2-



deoxy-D-galactose-2-



deoxy-D-glucose-L-



fucose-L-rhamnose


16243
L-kynurenine
35
0.2729
0.2215
316%


16276
Isobar-38-includes-N-
35
0.8281
0.3999
−4%



acetyl-L-methionine-5-



hydroxy-1H-indole-3-



acetic acid


16278
Isobar-35-includes-D-
35
0.585
0.3294
16%



arabinose-5-phosphate-D-



ribulose-5-phosphate-



alpha-D-ribose-5-



phosphate


16290
Metabolite - 4133
50
0.5451
0.3159
26%


16337
Metabolite - 4167
35
0.6297
0.3485
11%


16338
Metabolite - 4168
35
0.2445
0.2093
239%


16457
Metabolite - 4233
35
0.0367
0.1546
160%


16462
Metabolite - 4234
35
0.3867
0.2688
105%


16496
Metabolite - 4251
50
0.0612
0.1546
68%


16506
Metabolite - 4271
50
0.2168
0.2008
42%


16816
Metabolite - 4494
50
0.3938
0.2707
−8%


16818
Metabolite - 4495
50
0.2517
0.2126
28%


16819
Metabolite - 4496
50
0.1967
0.195
17%


16821
Metabolite - 4498
50
0.1936
0.195
37%


16822
Metabolite - 4499
50
0.0625
0.1546
57%


16823
Metabolite - 4500
50
0.2443
0.2093
159%


16824
iminodiacetic acid
50
0.5004
0.3001
23%


16827
Metabolite - 4502
50
0.0748
0.1546
5%


16829
Metabolite - 4503
50
0.0266
0.1546
60%


16831
Metabolite - 4504
50
0.012
0.1546
56%


16834
Metabolite - 4505
50
0.1015
0.1641
93%


16837
Metabolite - 4507
50
0.4492
0.2848
27%


16848
Metabolite - 4511
50
0.1687
0.1865
62%


16851
Metabolite - 4512
50
0.7087
0.3708
20%


16859
Metabolite - 4516
50
0.1197
0.1705
111%


16860
Metabolite - 4517
50
0.8131
0.3991
7%


16861
Metabolite - 4518
50
0.5277
0.308
47%


16862
Metabolite - 4519
50
0.0624
0.1546
120%


16863
Metabolite - 4520
50
0.4865
0.2937
−24%


16864
Metabolite - 4521
50
0.5658
0.3229
−21%


16865
Metabolite - 4522
50
0.0149
0.1546
54%


16866
Metabolite - 4523
50
0.0831
0.1546
43%


16867
Metabolite - 4524
50
0.9395
0.4275
−3%


16952
Metabolite - 4593
50
0.0167
0.1546
56%


16959
Metabolite - 4595
50
0.1416
0.1744
30%


17028
Metabolite - 4611
50
0.1674
0.1865
35%


17050
Metabolite - 4618
50
0.1343
0.1744
47%


17064
Metabolite - 4624
50
0.1424
0.1744
29%


17072
Metabolite - 4628
50
0.1106
0.1698
133%


17074
Metabolite - 4629
50
0.1355
0.1744
44%


17080
Metabolite - 4632
50
0.2873
0.2274
75%


17083
Metabolite - 4634
50
0.2324
0.2026
39%


17084
Metabolite - 4635
50
0.1653
0.1865
120%


17085
Metabolite - 4636
50
0.0414
0.1546
77%


17086
Metabolite - 4637
50
0.1528
0.1833
114%


17087
Metabolite - 4638
50
0.1281
0.1705
97%


17088
Metabolite - 4639
50
0.0915
0.1595
109%
















TABLE 11







Urine Metabolite Biomarkers to distinguish Lower Grade PCA from


Higher Grade PCA.

















% Change







in Higher


COMP_ID
COMPOUND
LIB_ID
p-value
q-value
PCA















53
glutamine
50
0.3616
0.4198
32%


54
tryptophan
35
0.0325
0.3021
47%


57
glutamic acid
50
0.3185
0.411
21%


59
histidine
50
0.2782
0.3951
37%


60
leucine
50
0.1497
0.3451
46%


64
phenylalanine
35
0.0392
0.3021
42%


418
guanine
50
0.0948
0.3377
54%


512
asparagine
50
0.1243
0.3401
60%


513
creatinine
35
0.0268
0.3021
34%


521
homogentisate
50
0.1224
0.3401
67%


527
lactate
50
0.9146
0.6009
−2%


528
alpha-keto-glutarate
35
0.5059
0.468
−17%


531
3-hydroxy-3-
50
0.3917
0.4342
24%



methylglutarate


541
4-hydroxyphenylacetate
50
0.8452
0.5813
6%


542
3-hydroxybutanoic acid
50
0.2058
0.3499
−59%


554
adenine
50
0.2549
0.3783
25%


555
adenosine
35
0.0081
0.3021
81%


563
alpha-L-sorbopyranose
50
0.1978
0.3499
94%


569
caffeine
35
0.029
0.3021
−53%


575
arabinose
50
0.0415
0.3021
72%


577
fructose
50
0.8863
0.591
7%


581
glucose
50
0.061
0.3283
52%


587
gluconic acid
50
0.1217
0.3401
64%


594
niacinamide
35
0.5535
0.4815
−9%


597
phosphoenolpyruvate
35
0.3699
0.4225
50%


605
uracil
50
0.1162
0.3401
35%


607
urocanic acid
35
0.7279
0.5417
11%


608
vitamin-B6
35
0.7072
0.5385
−15%


1101
3-methoxy-4-
50
0.0137
0.3021
55%



hydroxyphenylacetate


1107
allantoin
50
0.0607
0.3283
73%


1125
isoleucine
50
0.1449
0.3451
32%


1126
alanine
50
0.2233
0.3499
35%


1284
threonine
50
0.094
0.3377
38%


1299
tyrosine
50
0.0817
0.3308
39%


1302
methionine
35
0.0101
0.3021
54%


1303
malic acid
35
0.627
0.5038
11%


1366
trans-4-hydroxyproline
50
0.7014
0.5382
9%


1413
3-hydroxyphenylacetate
35
0.5846
0.4923
17%


1417
kynurenic acid
50
0.1657
0.3499
68%


1418
5-6-Dihydrothymine
35
0.075
0.3283
46%


1419
5-s-methyl-5-
35
0.3383
0.411
17%



thioadenosine


1431
(p-Hydroxyphenyl)lactic
50
0.4665
0.4614
42%



acid


1432
alphahydroxybenzeneacetic
35
0.7224
0.5417
6%



acid


1437
succinate
50
0.6047
0.497
13%


1444
DL-pipecolic acid
35
0.749
0.5497
18%


1480
guanidineacetic acid
35
0.0242
0.3021
99%


1493
ornithine
50
0.9781
0.6148
−1%


1494
5-oxoproline
50
0.3008
0.4095
24%


1498
N-6-trimethyl-l-lysine
35
0.1516
0.3464
37%


1505
orotic acid
50
0.2192
0.3499
38%


1508
pantothenic acid
35
0.3229
0.411
57%


1519
sucrose
50
0.9951
0.6181
0%


1557
3-methylglutaric acid
35
0.5659
0.4828
−11%


1558
4-acetamidobutyric acid
35
0.026
0.3021
60%


1559
5-6-dihydrouracil
50
0.1436
0.3451
26%


1560
L-methyldopa
35
0.597
0.497
14%


1564
citric acid
50
0.1013
0.3377
44%


1566
3-amino-isobutyrate
50
0.6838
0.5331
16%


1567
4-hydroxy-3-
50
0.0688
0.3283
53%



methoxymandelate


1568
4-hydroxymandelate
50
0.2224
0.3499
45%


1569
DL-beta-
35
0.4431
0.4524
17%



hydroxyphenylethylamine


1574
histamine
35
0.0188
0.3021
61%


1580
noradrenaline
50
0.2067
0.3499
50%


1585
N-acetyl-L-alanine
35
0.5273
0.4762
14%


1587
N-acetyl-L-leucine
35
0.1465
0.3451
41%


1591
N-acetyl-L-valine
35
0.2387
0.3625
50%


1592
N-acetylneuraminic acid
50
0.0338
0.3021
48%


1598
N-tigloylglycine
35
0.1685
0.3499
29%


1604
uric acid
35
0.3873
0.4336
5%


1640
ascorbic acid
50
0.6695
0.5267
54%


1648
serine
50
0.0526
0.3216
45%


1649
valine
50
0.1421
0.3451
26%


1708
7-8-dihydrofolic acid
35
0.1975
0.3499
23%


1778
gamma-glu-cys
35
0.4675
0.4614
47%


1827
riboflavine
35
0.2142
0.3499
183%


1860
3-nitro-L-tyrosine
35
0.974
0.6137
−1%


1868
cysteine
50
0.6881
0.534
23%


1898
proline
50
0.2767
0.395
46%


1899
quinolinic acid
50
0.1071
0.3377
40%


2078
pyrophosphate
50
0.3706
0.4225
44%


2092
catechol
35
0.018
0.3021
145%


2132
citrulline
50
0.0991
0.3377
35%


2183
thymidine
35
0.8751
0.5877
3%


2245
Metabolite - 294
35
0.3345
0.411
43%


2342
serotonin
35
0.0762
0.3283
34%


2734
gamma-L-glutamyl-L-
35
0.0437
0.3021
66%



tyrosine


2829
N-formyl-L-methionine
35
0.4526
0.4591
23%


2831
adenosine-3-5-cyclic-
35
0.008
0.3021
43%



monophosphate


3127
hypoxanthine
35
0.2239
0.3499
51%


3138
pyridoxamine-phosphate
35
0.8095
0.5733
5%


3147
xanthine
35
0.207
0.3499
60%


3155
3-ureidopropionic acid
35
0.1334
0.3451
67%


4966
xylitol
50
0.2152
0.3499
−31%


5493
Metabolite - 1059
35
0.8769
0.5877
−3%


5495
Metabolite - 1060
35
0.8529
0.5835
−2%


5514
Metabolite - 1081
35
0.026
0.3021
11%


5538
Metabolite - 1101
35
0.471
0.4614
59%


5664
Metabolite - 1101
35
0.6342
0.505
−15%


5687
Metabolite - 1110
35
0.306
0.411
23%


5697
acetylcarnitine-
35
0.8627
0.5857
−6%


5702
Metabolite - 1114
35
0.2517
0.3783
65%


5711
2-hydroxybutyric acid
35
0.7942
0.5658
−5%


5719
Metabolite - 1122
35
0.4991
0.4678
12%


5727
Metabolite - 1126
35
0.9422
0.6067
−2%


5797
Metabolite - 1186
35
0.2577
0.3783
30%


6137
Metabolite - 1212
35
0.1231
0.3401
36%


6147
Metabolite - 1216
35
0.5353
0.4784
−9%


6238
normetanephrine
50
0.2336
0.3587
17%


6253
Metabolite - 1283
35
0.4722
0.4614
35%


6278
Metabolite - 1289
35
0.4075
0.4428
13%


6329
urea
50
0.2047
0.3499
24%


6362
Metabolite - 1323-
35
0.1689
0.3499
56%



possible-p-cresol-sulfate


6398
Metabolite - 1335
35
0.4993
0.4678
12%


6405
Metabolite - 1338
35
0.4624
0.4614
−16%


6413
Metabolite - 1342-
35
0.1592
0.3499
28%



possible-



phenylacetylglutamine-or-



formyl-N-acetyl-5-



methoxykynurenamine


6421
Metabolite - 1345
35
0.2195
0.3499
71%


6437
Metabolite - 1349-
35
0.1055
0.3377
40%



possible-N-acetyl-8-O-



methyl-Neuraminic acid


6443
Metabolite - 1351
35
0.9453
0.6072
2%


6477
Metabolite - 1364
35
0.3548
0.419
−65%


6486
Metabolite - 1368
35
0.4304
0.4492
45%


6493
salicyluric acid
35
0.462
0.4614
−65%


6528
Metabolite - 1383-
35
0.4273
0.4492
−49%



possible-salicyluric-



glucuronide


6760
Metabolite - 1455
35
0.0092
0.3021
58%


6764
Metabolite - 1459
35
0.7767
0.5619
13%


6777
Metabolite - 1463
35
0.5723
0.485
−31%


6787
Metabolite - 1465
35
0.2726
0.3914
20%


6847
Metabolite - 1496
35
0.7359
0.5447
15%


6852
Metabolite - 1498
35
0.4113
0.4428
49%


6987
Metabolite - 1573
35
0.2236
0.3499
16%


7132
Metabolite - 1667
35
0.3277
0.411
−73%


7175
Metabolite - 1655
35
0.1087
0.3377
77%


7177
Metabolite - 1656
35
0.5561
0.4815
23%


7272
Metabolite - 1679
35
0.1129
0.3377
42%


7286
Metabolite - 1682
35
0.8923
0.5935
4%


7359
n-acetyl-L-aspartic acid
35
0.0709
0.3283
67%


7639
oxalic acid
35
0.1367
0.3451
25%


7650
Metabolite - 1834
35
0.4803
0.464
−21%


7660
Metabolite - 1839
35
0.9276
0.6009
−3%


7672
Metabolite - 1843
35
0.1049
0.3377
30%


7933
Metabolite - 1911
35
0.2835
0.4005
42%


8176
Metabolite - 1974
35
0.1493
0.3451
43%


8196
Metabolite - 1979-Cl-
35
0.7488
0.5497
−10%



adduct-of-isobar-19


8210
Metabolite - 1981
35
0.9643
0.6134
1%


8336
Metabolite - 2005
35
0.6224
0.5032
−11%


8644
Metabolite - 2051
35
0.5497
0.4815
8%


8677
Metabolite - 2056
35
0.1235
0.3401
24%


9007
Metabolite - 2108
35
0.6911
0.534
17%


9038
Metabolite - 2118
35
0.2102
0.3499
29%


9113
Metabolite - 2133
35
0.2101
0.3499
32%


9165
Metabolite - 2150
35
0.3592
0.4194
29%


9333
Metabolite - 2174
35
0.514
0.4716
15%


9334
Metabolite - 2175
35
0.3253
0.411
73%


9458
Metabolite - 2181
35
0.0095
0.3021
56%


10058
Metabolite - 2242
35
0.3061
0.411
−91%


10087
Metabolite - 2249
35
0.2194
0.3499
79%


10122
Metabolite - 2254
35
0.9247
0.6009
−2%


10136
Metabolite - 2034
35
0.3572
0.419
42%


10156
Metabolite - 2259
35
0.331
0.411
85%


10240
4-acetominophen-sulfate
35
0.6091
0.497
15%


10245
Metabolite - 2269-
35
0.715
0.5393
5%


10247
Metabolite - 2270
35
0.135
0.3451
−49%


10252
Metabolite - 2271
35
0.2042
0.3499
38%


10286
Metabolite - 2272
35
0.1989
0.3499
80%


10309
Metabolite - 2277
35
0.0163
0.3021
59%


10347
Metabolite - 2285
35
0.1474
0.3451
44%


10407
Metabolite - 2059
35
0.3262
0.411
22%


10424
Metabolite - 2292
35
0.0485
0.3188
−36%


10433
Metabolite - 2293-
35
0.3264
0.411
−91%



possible-O-



desmethylvenlafaxine-



glucuronide


10490
Metabolite - 2319
35
0.6803
0.5319
8%


10526
Metabolite - 2323
35
0.8122
0.5733
7%


10544
Metabolite - 2329
35
0.5016
0.4678
11%


10555
Metabolite - 2348
35
0.3735
0.4225
−36%


10570
Metabolite - 2366
35
0.5627
0.4824
13%


10629
Metabolite - 2386
35
0.2987
0.4088
19%


10644
Metabolite - 2387
35
0.374
0.4225
39%


10667
Metabolite - 2389
35
0.207
0.3499
−22%


10672
Metabolite - 2390
35
0.0744
0.3283
69%


10737
Isobar-1-includes-
35
0.9075
0.6009
−4%



mannose-fructose-



glucose-galactose-alpha-



L-sorbopyranose-Inositol-



D-allose-D--altrose-D-



psicone


10741
Isobar-2-includes-2-
35
0.7125
0.5393
−9%



aminoisobutyric acid-3-



amino-isobutyrate-2-



amino-butyrate-4-



aminobutanoic acid-



dimethylglycine-choline-


10743
Isobar-4-includes-
35
0.0298
0.3021
48%



Gluconic acid-DL-



arabinose-D-ribose-L-



xylose-DL-lyxose-D-



xylulose


10746
Isobar-6-includes-valine-
35
0.5275
0.4762
14%



betaine


10785
Metabolite - 2506
35
0.886
0.591
3%


10825
Metabolite - 2546
35
0.3726
0.4225
15%


10872
Metabolite - 2550
35
0.1131
0.3377
100%


10906
Metabolite - 2557-
35
0.7733
0.5619
−8%



possible-Pantoprazole-



metabolite


11053
Metabolite - 2567
35
0.0376
0.3021
42%


11085
Metabolite - 2588
35
0.3891
0.4336
64%


11110
Metabolite - 2591
35
0.0842
0.3353
−35%


11173
Metabolite - 2607
35
0.7772
0.5619
12%


11219
Metabolite - 2686
35
0.818
0.5733
5%


11264
Metabolite - 2698
35
0.2618
0.38
−43%


11271
Metabolite - 2700
35
0.4829
0.4648
29%


11292
Metabolite - 2703
35
0.0818
0.3308
25%


11299
Metabolite - 2706
35
0.4803
0.464
21%


11390
Metabolite - 2726
35
0.1731
0.3499
31%


11411
Metabolite - 2746
35
0.6339
0.505
−9%


11438
phosphate
50
0.2251
0.3499
27%


11484
Metabolite - 2752
35
0.077
0.3283
35%


11661
Metabolite - 2781
35
0.0671
0.3283
30%


11777
glycine
50
0.0787
0.3283
44%


11808
Metabolite - 2807
35
0.9564
0.6099
2%


11851
Metabolite - 2811
35
0.497
0.4678
28%


12025
cis-aconitic acid
50
0.8152
0.5733
12%


12055
galactose
50
0.9486
0.6079
3%


12102
o-phosphoethanolamine
50
0.4724
0.4614
25%


12104
Metabolite - 2852
35
0.2242
0.3499
199%


12109
Metabolite - 2853
35
0.6302
0.5048
14%


12129
beta-hydroxyisovaleric
50
0.0907
0.3377
43%



acid


12300
Metabolite - 2868
35
0.3468
0.4142
109%


12358
(1′R,1′S)_biopterin
35
0.8705
0.5877
3%


12426
Metabolite - 2416
35
0.329
0.411
44%


12463
Metabolite - 2893-
35
0.8121
0.5733
7%



possible-demethylated-



Rosiglitazone


12474
Metabolite - 2897
35
0.5015
0.4678
16%


12593
Metabolite - 2973
50
0.8428
0.5812
3%


12641
meso-erythritol
50
0.2553
0.3783
30%


12644
Metabolite - 3016
50
0.7026
0.5382
5%


12648
Metabolite - 3020
50
0.0318
0.3021
62%


12666
Metabolite - 3033
50
0.0908
0.3377
47%


12711
Metabolite - 3053
35
0.8572
0.5835
−8%


12720
Metabolite - 3056
35
0.1203
0.3401
30%


12765
inositol
50
0.986
0.6153
−1%


12770
Metabolite - 3090
50
0.0682
0.3283
25%


12771
Metabolite - 3091
50
0.1481
0.3451
83%


12795
Metabolite - 3113
50
0.9736
0.6137
−1%


12856
Metabolite - 3123
35
0.7353
0.5447
−8%


12902
Metabolite - 3127
35
0.5559
0.4815
14%


12904
Metabolite - 2457
35
0.7826
0.5634
10%


12924
Metabolite - 3131
35
0.3436
0.4141
31%


12938
Metabolite - 2459
35
0.662
0.5223
11%


13018
Metabolite - 3138
35
0.6504
0.5163
12%


13136
Metabolite - 3163-
35
0.3216
0.411
17%



possible-methylcytidine-



benserazide-Pyr-Gln-OH-



or-



glycerophosphocholine-


13153
Metabolite - 3169
35
0.264
0.3811
132%


13179
Metabolite - 3176
35
0.4698
0.4614
30%


13214
Metabolite - 3183-
35
0.1413
0.3451
45%



possible-gamma-L-



glutamyl-L-phenylalanine


13217
Metabolite - 3184
35
0.1112
0.3377
37%


13249
Metabolite - 3215
35
0.0274
0.3021
40%


13251
Metabolite - 3216
35
0.0408
0.3021
17%


13265
Metabolite - 3221
35
0.2155
0.3499
34%


13297
Metabolite - 3231
35
0.7164
0.5393
6%


13318
DL-indole-3-lactic acid
35
0.7541
0.5513
12%


13356
Metabolite - 3246-
35
0.0524
0.3216
76%



possible-Ala-GLy-glycyl-



sarcosine-or-ureido-



butyric acid


13459
Metabolite - 3305
35
0.1936
0.3499
47%


13484
Metabolite - 3309
35
0.491
0.4678
13%


13493
Metabolite - 3311-
35
0.1657
0.3499
−40%


13505
Metabolite - 3313
35
0.6134
0.4974
17%


13534
Metabolite - 3320-
35
0.559
0.4815
34%



possible-pimpinellin-or-



tetrahydroxybenzophenone


13545
Metabolite - 3322
35
0.0622
0.3283
90%


13589
Metabolite - 3327
35
0.2577
0.3783
37%


13594
Metabolite - 3329
35
0.0616
0.3283
149%


13704
Metabolite - 3355
35
0.6078
0.497
11%


13744
Metabolite - 3364
35
0.2939
0.4065
−19%


13775
Metabolite - 3370
35
0.1617
0.3499
35%


13791
Metabolite - 3373
35
0.3232
0.411
1137%


13803
Metabolite - 3377
35
0.4791
0.464
37%


13817
Metabolite - 3380
35
0.094
0.3377
53%


13820
beta-nicotinamide-
35
0.0454
0.3059
45%



mononucleotide


13847
Metabolite - 3387
35
0.3384
0.411
23%


13904
Metabolite - 3402
35
0.3627
0.4198
−38%


13968
Metabolite - 3409
35
0.9107
0.6009
4%


14036
Metabolite - 3427
35
0.1123
0.3377
58%


14066
Metabolite - 3433
35
0.4093
0.4428
12%


14084
Metabolite - 3436
35
0.8736
0.5877
2%


14115
Metabolite - 3440
35
0.8294
0.575
−5%


14125
Metabolite - 3443
35
0.0154
0.3021
−54%


14170
Metabolite - 3457
35
0.6072
0.497
−11%


14220
Metabolite - 3470
35
0.0626
0.3283
84%


14249
Metabolite - 3476
35
0.7481
0.5497
−9%


14368
Metabolite - 3489
35
0.1826
0.3499
−28%


14406
Metabolite - 3493
35
0.4363
0.4492
17%


14453
Metabolite - 3507
35
0.8289
0.575
−5%


14471
Metabolite - 3516
35
0.3193
0.411
−21%


14506
Metabolite - 3543
35
0.3275
0.411
111%


14539
Metabolite - 3564
35
0.2138
0.3499
107%


14595
Metabolite - 3576
35
0.1745
0.3499
63%


14640
Metabolite - 3604
35
0.9887
0.6156
0%


14641
Metabolite - 3605
35
0.5637
0.4824
24%


14731
Metabolite - 3659
35
0.5691
0.4839
14%


14732
Metabolite - 3660
35
0.627
0.5038
25%


14733
Metabolite - 3661
35
0.4336
0.4492
28%


14759
Metabolite - 3667
35
0.828
0.575
4%


14762
Metabolite - 3668
35
0.7262
0.5417
−6%


14766
Metabolite - 3670
35
0.8506
0.5835
−4%


14769
Metabolite - 3691
35
0.0162
0.3021
135%


14808
Metabolite - 3701
35
0.1711
0.3499
61%


14835
Metabolite - 3706
35
0.353
0.419
19%


14840
Metabolite - 3708
35
0.202
0.3499
184%


14907
Metabolite - 3734
35
0.1065
0.3377
49%


14983
Metabolite - 3754
35
0.9841
0.6153
−1%


14984
Metabolite - 3755
35
0.3568
0.419
−60%


15017
Metabolite - 3761
35
0.3351
0.411
15%


15057
Metabolite - 3771
35
0.7946
0.5658
−9%


15064
Metabolite - 3773
35
0.4963
0.4678
17%


15096
N-acetyl-D-glucosamine
50
0.0305
0.3021
81%


15121
Metabolite - 3786
35
0.9216
0.6009
−3%


15124
porphobilinogen
35
0.3291
0.411
22%


15125
(2-
35
0.0419
0.3021
25%



Aminoethyl)phosphonate


15128
DL-homocysteine
35
0.4331
0.4492
20%


15129
D-alanyl-D-alanine
35
0.2018
0.3499
27%


15130
diaminopimelic acid
35
0.0787
0.3283
49%


15131
dethiobiotin
35
0.4377
0.4492
74%


15187
Metabolite - 3800
35
0.1005
0.3377
82%


15197
Metabolite - 3802
35
0.3395
0.411
40%


15201
Metabolite - 3803
35
0.1397
0.3451
45%


15202
Metabolite - 3804
35
0.0505
0.3216
62%


15203
Metabolite - 3805
35
0.1828
0.3499
32%


15207
Metabolite - 3806
35
0.1977
0.3499
95%


15211
Metabolite - 3807
35
0.0352
0.3021
30%


15220
Metabolite - 3813
35
0.3153
0.411
26%


15228
Metabolite - 3817
35
0.0645
0.3283
62%


15240
Metabolite - 3824
35
0.837
0.5787
8%


15249
Metabolite - 3828
35
0.176
0.3499
43%


15251
Metabolite - 3830
35
0.5535
0.4815
20%


15253
Metabolite - 3832-
35
0.9729
0.6137
1%



possible-phenol-sulfate


15258
Metabolite - 3834-Peptide
35
0.5236
0.476
27%


15275
Metabolite - 3840
35
0.5876
0.4932
12%


15276
Metabolite - 3841
35
0.7884
0.5652
−12%


15278
Metabolite - 3843
35
0.1684
0.3499
48%


15284
Metabolite - 3847
35
0.9363
0.6044
2%


15294
Metabolite - 3855
35
0.9278
0.6009
−2%


15312
Metabolite - 3873
35
0.1113
0.3377
41%


15315
Metabolite - 3876
35
0.6801
0.5319
−17%


15324
Metabolite - 3878
35
0.9543
0.6099
−1%


15326
Metabolite - 3879
35
0.5214
0.4756
40%


15328
azelaic acid
35
0.5573
0.4815
27%


15335
mannitol
50
0.7785
0.5619
10%


15336
tartaric acid
35
0.1794
0.3499
69%


15356
Metabolite - 3886
35
0.3988
0.4403
17%


15359
Metabolite - 3887
35
0.8182
0.5733
6%


15365
sn-Glycerol-3-phosphate
50
0.5348
0.4784
23%


15374
Metabolite - 3893
35
0.4706
0.4614
15%


15382
Metabolite - 3898
35
0.287
0.4018
14%


15410
Metabolite - 3908
35
0.1311
0.3451
50%


15411
Metabolite - 3909
35
0.559
0.4815
−17%


15418
Metabolite - 3911
35
0.6533
0.517
7%


15496
agmatine
35
0.8254
0.575
−7%


15500
carnitine
35
0.191
0.3499
−31%


15529
Metabolite - 3951
35
0.0572
0.3283
34%


15532
Metabolite - 3952
35
0.3275
0.411
49%


15535
Metabolite - 3955
35
0.0891
0.3377
71%


15541
Metabolite - 3957
35
0.7242
0.5417
5%


15599
Metabolite - 3963
35
0.5152
0.4716
72%


15610
Metabolite - 3970
35
0.3254
0.411
24%


15620
Metabolite - 3973
35
0.2969
0.4084
94%


15626
Metabolite - 3977
35
0.2082
0.3499
65%


15636
Metabolite - 3981
35
0.3746
0.4225
49%


15641
Metabolite - 3986
35
0.6892
0.534
9%


15650
1-methyladenosine
35
0.0431
0.3021
54%


15667
2-isopropylmalic acid
50
0.9286
0.6009
−3%


15676
3-methyl-2-oxovaleric
35
0.7554
0.5513
−9%



acid


15677
3-methyl-L-histidine
35
0.0247
0.3021
50%


15679
xanthurenic acid
50
0.428
0.4492
25%


15681
4-Guanidinobutanoic acid
35
0.1785
0.3499
33%


15704
heptanedioic acid
35
0.0437
0.3021
42%


15716
L-beta-imidazolelactic
50
0.4297
0.4492
31%



acid


15730
suberic acid
35
0.5965
0.497
13%


15737
hydroxyacetic acid
50
0.1005
0.3377
38%


15743
N—N-dimethylarginine
35
0.1977
0.3499
25%


15753
hippuric acid
35
0.6063
0.497
11%


15778
benzoic acid
35
0.2541
0.3783
−35%


15804
maltose
50
0.4101
0.4428
−43%


15835
L-xylose
50
0.4221
0.4492
47%


15948
S-adenosyl-l-
35
0.1118
0.3377
40%



homocysteine


15964
D-arabitol
50
0.0578
0.3283
52%


16002
Metabolite - 3992-
35
0.5021
0.4678
−9%



possible-Cl-adduct-of-



Formate-dimer


16016
Metabolite - 3994
35
0.0348
0.3021
90%


16034
Metabolite - 4002
50
0.5041
0.468
17%


16071
Metabolite - 4020
50
0.0755
0.3283
44%


16082
Metabolite - 4027
50
0.1596
0.3499
33%


16107
lysine
50
0.6063
0.497
−30%


16175
Metabolite - 4092
35
0.4353
0.4492
22%


16197
Metabolite - 4112
35
0.122
0.3401
43%


16217
Metabolite - 4116
35
0.5789
0.4891
30%


16230
Isobar-29-includes-R—S-
35
0.2117
0.3499
135%



hydroorotic acid-5-6-



dihydroorotic acid


16232
Isobar-17-includes-
35
0.4014
0.4413
−23%



arginine-N-alpha-acetyl-



ornithine


16233
Isobar-13-includes-5-keto-
35
0.3895
0.4336
63%



D-gluconic acid-2-keto-L-



gulonic acid-D-glucuronic



acid-D-galacturonic acid


16235
Isobar-19-includes-D-
35
0.5538
0.4815
22%



saccharic acid-1-5-



anhydro-D-glucitol-2-



deoxy-D-galactose-2-



deoxy-D-glucose-L-



fucose-L-rhamnose


16243
L-kynurenine
35
0.2602
0.3798
353%


16276
Isobar-38-includes-N-
35
0.3469
0.4142
−19%



acetyl-L-methionine-5-



hydroxy-1H-indole-3-



acetic acid


16278
Isobar-35-includes-D-
35
0.874
0.5877
−3%



arabinose-5-phosphate-D-



ribulose-5-phosphate-



alpha-D-ribose-5-



phosphate


16290
Metabolite - 4133
50
0.8566
0.5835
−7%


16337
Metabolite - 4167
35
0.9854
0.6153
−1%


16338
Metabolite - 4168
35
0.2875
0.4018
183%


16457
Metabolite - 4233
35
0.0702
0.3283
115%


16462
Metabolite - 4234
35
0.7005
0.5382
30%


16496
Metabolite - 4251
50
0.0239
0.3021
99%


16506
Metabolite - 4271
50
0.7894
0.5652
9%


16816
Metabolite - 4494
50
0.4086
0.4428
−7%


16818
Metabolite - 4495
50
0.7053
0.5385
8%


16819
Metabolite - 4496
50
0.4299
0.4492
10%


16821
Metabolite - 4498
50
0.9186
0.6009
3%


16822
Metabolite - 4499
50
0.132
0.3451
42%


16823
Metabolite - 4500
50
0.5079
0.4682
59%


16824
iminodiacetic acid
50
0.1695
0.3499
60%


16827
Metabolite - 4502
50
0.0356
0.3021
6%


16829
Metabolite - 4503
50
0.1744
0.3499
30%


16831
Metabolite - 4504
50
0.0255
0.3021
47%


16834
Metabolite - 4505
50
0.1844
0.3499
68%


16837
Metabolite - 4507
50
0.9737
0.6137
1%


16848
Metabolite - 4511
50
0.5473
0.4815
22%


16851
Metabolite - 4512
50
0.5346
0.4784
−25%


16859
Metabolite - 4516
50
0.1479
0.3451
95%


16860
Metabolite - 4517
50
0.9134
0.6009
−3%


16861
Metabolite - 4518
50
0.5481
0.4815
45%


16862
Metabolite - 4519
50
0.0417
0.3021
147%


16863
Metabolite - 4520
50
0.49
0.4678
−23%


16864
Metabolite - 4521
50
0.5999
0.497
−17%


16865
Metabolite - 4522
50
0.0317
0.3021
45%


16866
Metabolite - 4523
50
0.1397
0.3451
35%


16867
Metabolite - 4524
50
0.4657
0.4614
41%


16952
Metabolite - 4593
50
0.1068
0.3377
32%


16959
Metabolite - 4595
50
0.206
0.3499
26%


17028
Metabolite - 4611
50
0.191
0.3499
30%


17050
Metabolite - 4618
50
0.7146
0.5393
−14%


17064
Metabolite - 4624
50
0.4442
0.4524
15%


17072
Metabolite - 4628
50
0.6112
0.4971
29%


17074
Metabolite - 4629
50
0.2339
0.3587
32%


17080
Metabolite - 4632
50
0.3386
0.411
64%


17083
Metabolite - 4634
50
0.2892
0.402
32%


17084
Metabolite - 4635
50
0.9283
0.6009
−6%


17085
Metabolite - 4636
50
0.1467
0.3451
50%


17086
Metabolite - 4637
50
0.1763
0.3499
99%


17087
Metabolite - 4638
50
0.4336
0.4492
37%


17088
Metabolite - 4639
50
0.2348
0.3587
58%









Example 5
Random Forest Analysis for the Classification of Tissue Samples
The data obtained in Example 1 concerning the tissue samples was used to create a random forest model. Random Forest Analysis was carried out on the data obtained from tissue samples in Example 1 to classify them as Normal (N), Localized (i.e. lower grade) cancer tumor (T) or Metastatic tumor (M). The first analysis resulted in 90.5% correct classification of the three tissue types. The metastatic tumors were correctly classified 100% of the time while the normal tissue and the localized prostate cancer tumors were correctly classified 87% and 83%, respectively (Table 12).







TABLE 12







Confusion matrix for metastatic (M), normal prostate (N) and


localized prostate cancer tumor (T) tissue types.










Predicted Tissue Type













Metastatic
Normal
Localized




Tumor
Tissue
Tumor
error
















Actual
Metastatic Tumor
14
0
0
0.00


Tissue
(M)


Type
Normal Tissue (N)
0
14
2
0.13



Localized Tumor (T)
0
2
10
0.17





OOB Error = 9.5%






Based on the OOB Error rate of 9.5%, the Random Forest model that was created could be used to predict whether a subject has a metastatic tumor (M), a localized tumor (T), or normal tissue (N) with about 90.5% accuracy from analysis of the levels of the biomarkers in samples from the subject.
The importance plot is shown in FIG. 1. The important metabolites for this classification are listed in Table 13.







TABLE 13







Most important biomarker metabolites to distinguish N, T, M tissue


types.










Metabolite
Library







n-hexadecanoic acid (palmitate)
50



tetradecanoic acid (myristate)
50



inosine
61



octadecanoic acid (stearate(
50



3-amino-isobutyrate
50



n-dodecanoate (laurate)
50



(2-aminoethyl)phosphonate
61



Metabolite - 3778
61



glycerol
50



(p-hydroxyphenyl)lactic acid
50



palmitoleic acid
50



N-acetyl-D-galactosamine
50



Metabolite - 3102
50



meso-erythritol
50



Metabolite - 1597
61



uracil
50



uridine
61



Metabolite - 4075
50



Isobar - 24 includes L-arabitol & adonitol
61



Metabolite - 2867
61



Metabolite - 4620
61



sn-glycerol-3-phosphate
50



Metabolite - 4117 (possible-propranolol or 2-
61



heptyl-3-hydroxy-quinolone



Metabolite - 1114
61



DL-homocysteine
61



leucine
50



xanthine
61



Metabolite - 1576
61



Metabolite - 2973
50



Metabolite - 3810
61










Based on this analysis one sample appeared to be an outlier. Sample T3, which was reported as localized prostate tumor tissue, appears to be an outlier. From the random forest comparing all three tissue types, 80% of the trees in the random forest classified T3 as an “N” or normal while only 17% correctly classed it as “T” and only 3% classified it as “M” or metastatic. This result indicates that the sample may be a mixture of normal and cancerous tissue or that the sample is at an early stage of cancer.
Random Forest Analysis was also carried out on the tissue samples from the prostate to classify them as Normal prostate (N) or Localized prostate cancer tumor (T). This analysis resulted in 86% correct classification of the two tissue types. The normal tissue and the localized prostate cancer tumors were correctly classified 87% and 83% respectively (Table 14).







TABLE 14







Confusion matrix comparing Normal prostate tissue (N) with


Localized prostate tumor tissue (T).










Predicted




Tissue Type











Normal
Localized




Tissue
Tumor
error















Actual
Normal Tissue (N)
14
2
0.13


Tissue
Localized Tumor
2
10
0.17


Type
(T)





OOB Error = 14%






Based on the OOB Error rate of 14%, the Random Forest model that was created could be used to predict whether a subject has normal tissue (N), or localized tumor (T) tissue with about 86% accuracy from analysis of the levels of biomarkers in samples from the subject.
The important metabolites for this classification are listed in Table 15 and shown in the importance plot in FIG. 2.







TABLE 15







Most important biomarker metabolites to distinguish Normal prostate


tissue (N) and Cancerous prostate tumor tissue (T).










Metabolite
Library







N-acetyl-D-galactosamine
50



Metabolite - 3778
61



uridine
61



Metabolite - 4117 possible propanolol or 2-
61



heptyl-3-hydroxy-quinolone



Metabolite - 1114
61



Metabolite - 3810
61



DL-homocysteine
61



Metabolite - 3094
50



Metabolite - 4616
61



Metabolite - 1576
61



Metabolite - 3139
61



sn-glycerol-3-phospate
50



Metabolite - 2973
50



carnitine
61



Metabolite - 2041
61



Isobar 3 includes inositol-1-phosphate,
61



mannose-6-phospate, glucose-6-phosphate, D-



mannose-1-phoaphate, alpha-D-glucose-1-



phosphate



kynurenic acid
61



n-hexadecanoic acid (palmitate)
50



cysteine
50



Metabolite - 4027
50



Metabolite - 3027
50



glutamic acid
50



Metabolite - 2688
61



Metabolite - 1111 possible
61



methylnitronitrosoguanidine or ethyl-



thiocarbamoylacetate



Metabolite - 2055
61



Metabolite - 3176 possible creatine
61



uracil
50



glycine
50



Metabolite - 3165
61



Metabolite - 1595 possible glutathione-
61



metabolite










Since the metastatic tumors were obtained from sites distal to the prostate, we determined if these tissues were distinguished from the normal and cancerous prostate tissue due to the metastasis or due to the location of the tumor. To test this, the metastatic tumor tissue samples from liver were compared with the non-liver metastatic tumor tissues using Random Forest. The confusion matrix resulting from this analysis is provided in Table 16 and the results are essentially random chance; the liver and non-liver origins of the tumors appear to be indistinguishable. Thus, the classification of the metastatic tumor tissue is based on the metabolite biomarkers for metastasis and not on the source tissue of the metastatic tumor.







TABLE 16







Confusion matrix comparing metastatic tumors from liver tissue with


metastatic tumors from non-liver tissue.










Predicted




Tissue Source











Liver
Non-liver
error

















Actual
Liver
5
3
0.38



Tissue
Non-
5
5
0.50



Source
liver







OOB Error = 43%






Based on the OOB Error rate of 43%, the Random Forest model that was created could be used to predict whether a subject has a metastatic tumor from liver tissue, compared to non-liver tissue, with about 57% accuracy from analysis of the levels of biomarkers in liver tissue samples from the subject, but the Error Rate may essentially be random chance and may indicate that the source (i.e. liver or non-liver) of the tumor tissue is not predicted by these biomarkers.
Example 6
Random Forest Analysis for the Classification of Urine Samples from Control Subjects, Subjects with Low Grade PCA and Subjects with High Grade PCA
Random Forest Analysis was carried out on the data obtained from urine samples in Example 4 to classify them as Non-cancer (Control) or Prostate cancer. The control samples were urine obtained from subjects with a Gleason score (major) of 0 or from prostate cancer (PCA) subjects with a Gleason score (major)>=4. The analysis resulted in 63% correct classification of the urine sample types. The control subjects were correctly classified 62% of the time while the subjects with prostate cancer (PCA) were correctly classified 64% of the time (Table 17).







TABLE 17







Confusion matrix for control vs PCA in Urine.










Predicted












Control
PCA
error

















Actual
Control
33
20
0.38




PCA
5
9
0.36







OOB Error = 37%






Based on the OOB Error rate of 37%, the Random Forest model that was created could be used to predict whether a subject has prostate cancer (PCA), compared to being cancer-free, with about 63% accuracy from analysis of the levels of biomarkers in urine from the subject.
The importance plot is shown in FIG. 3. The important metabolites for this classification are listed in Table 18.







TABLE 18







Most important urine biomarker metabolites to distinguish Control


from PCA.










Metabolite
Library







(2-aminoethyl)phosphonate
35



Metabolite - 2051
35



Metabolite - 3805
35



Guanidineacetic acid
35



catechol
35



N-acetyl-L-valine
35



DL-beta-hydroxyphenylethylamine
35



N-acetyl-D-glucosamine
50



Metabolite - 1974
35



Metabolite - 4636
50



Metabolite - 2811
35



Metabolite - 3176
35



Metabolite - 1979
35



histamine
35



alpha-L-sorbopyranose
50



xylitol
50



Metabolite - 4504
50



Metabolite - 2285
35



3-methoxy-4-hydroxyphenylacetate
50



Metabolite - 2181
35



Metabolite - 1455
35



adenosine
35



Isobar 6: includes valine & betaine
35



Metabolite - 3169
35



Metabolite - 3470
35



Metabolite - 4502
50



Metabolite - 2746
35



Metabolite - 4503
50



Metabolite - 3476
35



Metabolite - 3443
35










Random Forest Analysis was also carried out on the biomarkers identified in Example 4 from urine samples to classify them as lower grade prostate cancer (Gleason score major 3) or higher grade prostate cancer (Gleason score major>=4). In this analysis resulted in 61% correct classification of the two cancer grades. The lower grade and the higher grade prostate cancers were correctly classified 58% and 71% respectively (Table 19).







TABLE 19







Confusion matrix comparing urine from subjects with lower grade


prostate cancer and higher grade prostate cancer.










Predicted




Grade











Low
High
error

















Actual
Low
25
18
0.42



Grade
High
4
10
0.29







OOB Error = 39%






Based on the OOB Error rate of 39%, the Random Forest model that was created could be used to predict whether a subject has a lower grade prostate cancer or a higher grade prostate cancer with about 61% accuracy from analysis of the levels of biomarkers in urine from the subject.
The importance plot is shown in FIG. 4. The important metabolites for this classification are listed in Table 20.







TABLE 20







Most important urine biomarker metabolites to distinguish subjects


with lower grade prostate cancer and higher grade prostate cancer.










Metabolite
Library







Metabolite - 3805
35



Histamine
35



Metabolite - 1455
35



Catechol
35



xylitol
50



Metabolite - 4636
50



Metabolite - 3691
35



Adenosine
35



Glycine
50



Metabolite - 3661
35



Metabolite - 3955
35



Methionine
35



Isobar 6 includes valine, betaine
35



guanidineacetic acid
35



Metabolite - 3817
35



N-acetyl-D-glucosamine
50



Metabolite - 3806
35



Metabolite - 2277
35



3-methoxy-4-hydroxyphenylacetate
50



Metabolite - 4502
50



Metabolite - 4519
50



Guanine
50



Metabolite - 2181
35



Alpha-L-sorbopyranose
50



Metabolite - 2270
35



Metabolite - 1498
35



Metabolite - 3443
35



tryptophan
35



Metabolite - 2051
35



gamma-L-glutamy-L-tyrosine
35










Example 7
Random Forest Analysis for the Classification of Plasma Samples from Control Subjects, Subjects with Lower Grade PCA and Subjects with Higher Grade PCA
Random Forest Analysis was carried out on data obtained in Example 3 from plasma samples to classify them as Non-cancer (Control) or Prostate cancer. The control samples were plasma obtained from subjects with a Gleason score (major) of 0 or from prostate cancer (PCA) subjects with a Gleason score (major) 3. The analysis resulted in 65% correct classification of the plasma sample types. The control subjects were correctly classified 68% of the time while the subjects with prostate cancer (PCA) were correctly classified 60% of the time (Table 21).







TABLE 21







Confusion matrix for Control vs Lower Grade PCA in Plasma.










Predicted












Control
PCA
error

















Actual
Control
36
17
0.32




PCA
17
26
0.40







OOB Error = 35%






Based on the OOB Error rate of 35%, the Random Forest model that was created could be used to predict whether a subject has a lower grade prostate cancer or does not have prostate cancer with about 65% accuracy from analysis of the levels of biomarkers in plasma from the subject.
The importance plot is shown in FIG. 5. The important metabolites for this classification are listed in Table 22.







TABLE 22







Most important plasma biomarker metabolites to distinguish Control


from Lower Grade PCA.










Metabolite
Library







Metabolite - 1185
35



5-oxoproline
50



IHWESASLLR
35



Metabolite - 3765
35



Metabolite - 2753
35



Hydroxyproline form of bradykinin
35



D-alany-D-alanine
35



Metabolite - 5437
50



Metabolite - 2256
35



Metabolite - 5366
50



Metabolite - 4611
50



Alpha keto glutarate
35



Metabolite - 3167
35



Alpha-tocopherol
50



Metabolite - 3377
35



Metabolite - 1127
35



Iminodiacetic acid
50



Trans-4-hydroxyproline
50



Metabolite - 2111
35



Metabolite - 2853
35



Metabolite - 2185
35



Metabolite - 3030
50



Metabolite - 3017
50



Metabolite - 1083
35



N-acetyl-L-valine
35



Metabolite - 1597
35



Creatinine
35



Isobar 36 includes D-sorbitol-6-phosphate,
35



mannitol-1-phosphate



Metabolite - 2914
50



Pyridoxal-phosphate
35










Random Forest Analysis was also carried out on the biomarkers from plasma samples in Example 3 to classify them as control (Gleason score major 0) or higher grade prostate cancer (Gleason score major>=4, PCA). In this analysis resulted in 73% correct classification of the plasma sample types. The control and the higher grade prostate cancers were correctly classified 58% and 71% respectively (Table 23).







TABLE 23







Confusion matrix comparing plasma from subjects without prostate


cancer (Control) and with higher grade prostate cancer (High PCA).










Predicted













High




Control
PCA
error

















Actual
Control
36
17
0.32




High PCA
2
13
0.07







OOB Error = 27%






Based on the OOB Error rate of 27%, the Random Forest model that was created could be used to predict whether a subject has a higher grade prostate cancer or does not have prostate cancer with about 63% accuracy from analysis of the levels of biomarkers in plasma from the subject.
The importance plot is shown in FIG. 6. The important biomarker metabolites for this classification are listed in Table 24.







TABLE 24







Most important plasma biomarker metabolites to distinguish subjects


without prostate cancer from those with higher grade prostate cancer.










Metabolite
Library







Metabolite - 1185
35



Metabolite - 3377
35



Metabolite - 2329
35



Metabolite - 3603
35



Metabolite - 1127
35



Metabolite - 3305
35



Metabolite - 2389
35



Metabolite - 3088
50



Trans-4-hydroxyproline
50



Metabolite - 1104
35



Isobar 17 includes arginine, N-alpha-acetyl-
35



ornithine



Metabolite - 4769
50



Metabolite - 2141
35



Metabolite - 3030
50



Metabolite - 2867
35



Metabolite - 3707
35



Metabolite - 3098
50



Palmitoleic acid
50



Metabolite - 2711
35



Tetradecanoic acid
50



Metabolite - 2287
35



Metabolite - 2407
35



DL-indole-3-lactic acid
50



Metabolite - 1286
35



Heptadecanoic acid
50



Metabolite - 3033
50



5-oxoproline
50



Metabolite - 3576
35



Tartaric acid
35



Metabolite - 1831 possible Cl adduct of
35



citrulline










Random Forest Analysis was also carried out on the biomarkers from plasma samples to classify them as lower grade prostate cancer (Gleason score major 3) or higher grade prostate cancer (Gleason score major>=4). This analysis resulted in 67% correct classification of the two cancer grades. The lower grade and the higher grade prostate cancers were correctly classified 65% and 71% respectively (Table 25).







TABLE 25







Confusion matrix classifying plasma from subjects with lower grade


prostate cancer and higher grade prostate cancer.










Predicted




Grade











Low
High
error

















Actual
Low
28
15
0.35



Grade
High
4
10
0.29







OOB Error = 33%






Based on the OOB Error rate of 33%, the Random Forest model that was created could be used to predict whether a subject has a lower grade prostate cancer or a higher grade prostate cancer with about 67% accuracy from analysis of the levels of biomarkers in plasma from the subject.
The importance plot is shown in FIG. 7. The important metabolites for this classification are listed in Table 26.







TABLE 26







Most important plasma biomarker metabolites to distinguish subjects


with lower grade prostate cancer and higher grade prostate cancer.










Metabolite
Library







Metabolite - 2329
35



Heptadecanoic acid
50



Metabolite - 3088
50



Metabolite - 3322
35



Palmitoleic acid
50



Isobar 6 includes valine and betaine
35



Tetradecanoic acid
50



Pyridoxal-phosphate
35



4-methyl-2-oxopentanoate
50



Metabolite - 3534
35



Metabolite - 2711
35



Isobar 17 includes arginine, N-alpha-acetyl-
35



ornithine.



Octadecanoic acid
50



Caffeine
35



Metabolite - 2389
35



Metabolite - 3377
35



Metabolite - 3305
35



Leucine
50



Metabolite - 2407
35



Metabolite - 3900
35



Metabolite - 3992 possible Cl adduct of formate
35



dimmer



Metabolite - 3089
50



Trans-4-hydroxypyruvate
50



Metabolite - 5437
50



N-hexadecanoic acid
50



Paraxanthine
35



Metabolite - 3603
35



M2130
35



Oleic acid
50



Metabolite - 1286
35










Example 8
Analytical Characterization of Unnamed Biomarkers Compounds
Table 27 below includes analytical characteristics of each of the isobars and the unnamed metabolites listed in Tables 1-26 above. The table includes, for each listed Isobar and Metabolite, the retention time (RT), retention index (RI), mass, quant mass, and polarity obtained using the analytical methods described above. “Mass” refers to the mass of the C12 isotope of the parent ion used in quantification of the compound. The values for “Quant Mass” give an indication of the analytical method used for quantification: “Y” indicates GC-MS and “1” indicates LC-MS. “Polarity” indicates the polarity of the quantitative ion as being either positive (+) or negative (−).







TABLE 27







Analytical Characteristics of Isobars and Unnamed Metabolites.












COMPOUND
RT
RI
MASS
QUANT_MASS
Polarity















Isobar 1 includes mannose,
1.45
1481.0
215
1
−


fructose, glucose, galactose,


alpha-L-sorbopyranose, Inositol,


D-allose


Isobar 13 includes 5-keto-D-
1.40
1530.0
193.1
1
−


gluconic acid, 2-keto-L-gulonic


acid, D-glucuronic acid


Isobar 17 includes arginine, N-
1.49
1620.0
175.2
1
+


alpha-acetyl-ornithine


Isobar 18 includes D-fructose 1-
1.33
1475.0
259.1
1
−


phosphate, beta-D-fructose 6-


phosphate


Isobar 19 includes D-saccharic
1.55
1700.0
209
1
−


acid, 2-deoxy-D-galactose, 2-


deoxy-D-glucose, L-fucose, L-


rhamnose


Isobar 2 includes 3-amino-
1.60
1671.0
104.1
1
+


isobutyrate, 2-amino-butyrate, 4-


aminobutanoic acid,


dimethylglycine, choline


Isobar 20 includes fumaric acid,
4.45
4800.0
160.9
1
−


3-methyl-2-oxobutanoate


Isobar 21 includes gamma-
1.59
1620.0
263.1
1
+


aminobutyryl-L-histidine, L-


anserine


Isobar 22 includes glutamic acid,
1.55
1635.0
148
1
+


O-acetyl-L-serine


Isobar 24 includes L-arabitol,
1.43
1545.0
153.1
1
+


adonitol


Isobar 25 includes L-gulono-1,4-
1.67
1615.0
222.9
1
−


lactone, glucono-gamma-lactone


Isobar 27 includes L-kynurenine,
8.23
8470.0
209.1
1
+


alpha-2-diamino-gamma-


oxobenzenebutanoic acid


Isobar 29 includes R,S-
2.17
2095.0
157.1
1
−


hydroorotic acid, 5,6-


dihydroorotic acid


Isobar 3 includes inositol 1-
1.45
1467.0
304.7
1
−


phosphate, mannose 6-


phosphate, glucose 6-phosphate,


D-mannose 1-phosphate, alpha-


D-glucose 1-phosphate, alpha-D-


galactose 1 phosphate


Isobar 30 includes maltotetraose,
1.67
1770.0
710.8
1
−


stachyose


Isobar 31 includes maltotriose,
1.64
1752.0
548.8
1
−


melezitose


Isobar 32 includes N-acetyl-D-
1.57
1685.0
222
1
+


glucosamine, N-acetyl-D-


mannosamine


Isobar 36 includes D-sorbitol 6-
1.37
1470.0
261.1
1
−


phosphate, mannitol-1-phosphate


Isobar 38 includes N-acetyl-L-
9.12
9220.0
192
1
+


methionine, 5-hydroxy-1H-indole-


3-acetic acid


Isobar 4 includes Gluconic acid,
1.52
1587.0
195
1
−


DL-arabinose, D-ribose, L-xylose,


DL-lyxose, D-xylulose


Isobar 40 includes Maltotetraose,
1.67
2282.0
710.8
1
−


stachyose


Isobar 5 includes asparagine,
1.50
1395.0
133.1
1
+


ornithine


Isobar 6 includes valine, betaine
2.13
2160.0
118.1
1
+


Isobar 9 includes sucrose, beta-
1.60
1605.0
386.9
1
−


D-lactose, D-trehalose, D-


cellobiose, D-Maltose, palatinose,


melibiose, alpha-D-lactose


Metabolite - 1069 - possible
12.55
14450.0
367.2
1
−


dehydroepiandrosterone sulfate


Metabolite - 1070
9.00
9169.0
378.3
1
+


Metabolite - 1085 - possible
15.82
15964.0
288.1
1
+


isolobinine or 4-aminoestra-


1,3,5(10)-triene-3,17beta-diol


Metabolite - 1086
4.56
4811.0
294.1
1
+


Metabolite - 1088
13.12
14225.0
369.1
1
−


Metabolite - 1104
2.43
2410.0
201
1
−


Metabolite - 1110
11.66
11841.0
269.1
1
−


Metabolite - 1111 - possible
2.69
2700.0
148.1
1
+


methylnitronitrosoguanidine or


ethyl thiocarbamoylacetate


Metabolite - 1113 - possible
4.91
5290.0
204.2
1
+


acetylcarnitine


Metabolite - 1114
2.19
2198.0
104.1
1
+


Metabolite - 1116
4.20
4780.0
103.4
1
−


Metabolite - 1121
16.29
16429.0
303.3
1
+


Metabolite - 1122
4.45
4701.0
233.1
1
+


Metabolite - 1126
3.04
3188.0
175.1
1
+


Metabolite - 1127
12.18
12369.0
363.1
1
+


Metabolite - 1129
5.16
5419.0
260.1
1
+


Metabolite - 1133-retired Na
1.63
1636.0
315
1
+


adduct of EDTA


Metabolite - 1142-possible 5-
8.54
8739.0
163
1
−


hydroxypentanoate or beta-


hydroxyisovaleric acid


Metabolite - 1183
8.56
8765.0
365.8
1
+


Metabolite - 1185
8.70
9150.0
506.8
1
+


Metabolite - 1186
8.83
9000.0
529.6
1
+


Metabolite - 1187
8.80
9017.0
559.9
1
+


Metabolite - 1188
8.83
9017.0
619.9
1
+


Metabolite - 1203 - possible
9.11
9288.0
510.2
1
+


HXGXA


Metabolite - 1208
15.33
15494.0
319.4
1
−


Metabolite - 1211 - possible
9.90
9800.0
606.5
1
+


IHWESASLLR


Metabolite - 1215
8.96
9390.0
550.1
1
+


Metabolite - 1216
1.60
1631.4
343.9
1
−


Metabolite - 1220
15.24
15402.5
319.2
1
+


Metabolite - 1244
15.28
15436.8
343.4
1
−


Metabolite - 1248 - possible
8.06
8275.4
302.3
1
+


avermectin aglycone


Metabolite - 1283
9.04
9244.5
434.8
1
+


Metabolite - 1286
14.41
14579.8
229
1
+


Metabolite - 1288
2.11
2120.5
302
1
−


Metabolite - 1289
8.96
9139.7
338.4
1
+


Metabolite - 1303
9.01
9178.0
527.8
1
+


Metabolite - 1323-possible p-
9.31
10000.0
187
1
−


cresol sulfate


Metabolite - 1327 - possible
13.22
13300.0
585.4
1
+


bilirubin


Metabolite - 1329
2.69
2791.0
210.1
1
+


Metabolite - 1330
10.67
11097.7
436.3
1
+


Metabolite - 1333
3.05
3794.0
321.9
1
+


Metabolite - 1335
8.74
9162.2
367.2
1
+


Metabolite - 1338
10.76
11193.0
241.1
1
−


Metabolite - 1342 - possible
9.04
9459.4
265.2
1
+


phenylacetylglutamine or formyl-


N-acetyl-5-methoxykynurenamine


Metabolite - 1349
3.50
3876.0
323.9
1
+


Metabolite - 1351
1.77
1936.5
177.9
1
+


Metabolite - 1364
10.35
10765.1
397.2
1
+


Metabolite - 1368
8.18
8607.4
184.1
1
+


Metabolite - 1383 - possible
8.66
9077.9
370.1
1
−


salicyluric glucuronide


Metabolite - 1389 - possible
13.62
14111.3
425.3
1
−


glucuronide form of X-1359


Metabolite - 1392
10.90
11350.3
415.2
1
+


Metabolite - 1394 - possible
12.28
12752.0
423.2
1
+


Losartan


Metabolite - 1455
2.38
2350.0
131.1
1
+


Metabolite - 1457
1.59
1675.0
188.2
1
+


Metabolite - 1465
3.45
3600.0
162.1
1
+


Metabolite - 1496
1.53
1562.0
133
1
−


Metabolite - 1497
13.87
14031.5
332.2
1
+


Metabolite - 1498
1.56
1650.0
143.1
1
−


Metabolite - 1573
1.63
1669.0
170.9
1
−


Metabolite - 1575
2.25
2243.5
219.1
1
+


Metabolite - 1576
2.51
2530.0
247.1
1
+


Metabolite - 1593
2.67
2690.0
395.9
1
−


Metabolite - 1594
3.15
3325.0
263.1
1
+


Metabolite - 1595 - possible
3.14
3400.0
290.1
1
+


glutathione metabolite


Metabolite - 1596
3.66
3902.0
185
1
−


Metabolite - 1597
3.66
4100.0
265.9
1
+


Metabolite - 1608
8.08
8253.0
348.1
1
−


Metabolite - 1609
8.31
8529.0
378
1
+


Metabolite - 1616
12.73
12910.3
331.2
1
+


Metabolite - 1653
16.84
16977.0
454.3
1
+


Metabolite - 1655
1.31
1374.0
107
1
+


Metabolite - 1656
1.46
1509.0
154.9
1
−


Metabolite - 1679
8.52
8705.8
283.1
1
−


Metabolite - 1680
8.50
8681.0
851.1
1
+


Metabolite - 1682
8.78
8961.0
339.1
1
−


Metabolite - 1713
2.73
3050.0
174
1
−


Metabolite - 1718
8.43
8390.0
457.9
1
+


Metabolite - 1817
1.37
1552.3
252
1
+


Metabolite - 1819
1.36
1539.6
244.8
1
−


Metabolite - 1829
1.43
1600.0
135
1
−


Metabolite - 1831 - possible Cl
1.46
1638.7
209.9
1
−


adduct of citrulline


Metabolite - 1834
1.64
1960.0
104
1
−


Metabolite - 1835
1.86
1999.3
152.1
1
−


Metabolite - 1836
2.10
2215.5
205.9
1
−


Metabolite - 1911
11.42
11799.6
464.1
1
+


Metabolite - 1914
10.35
10719.8
239.1
1
+


Metabolite - 1915
14.37
14798.6
507.2
1
−


Metabolite - 1963
13.15
13550.8
464.1
1
+


Metabolite - 1970
12.88
13271.2
852.9
1
+


Metabolite - 1974
5.93
6300.0
160.2
1
+


Metabolite - 1975
5.95
6093.0
344
1
+


Metabolite - 1977
3.56
4060.0
260.9
1
+


Metabolite - 1979 - Cl adduct of
1.52
1690.3
199
1
−


isobar 19


Metabolite - 1980
13.20
13250.0
391.1
1
+


Metabolite - 1981
7.94
8150.0
158.1
1
+


Metabolite - 1988
11.14
11515.0
190.1
1
+


Metabolite - 2005
8.62
9048.0
232.1
1
+


Metabolite - 2027
1.56
1729.3
184.1
1
+


Metabolite - 2036
14.30
14300.0
616.3
1
+


Metabolite - 2041
13.84
14198.1
246.3
1
+


Metabolite - 2051
1.45
1634.0
309
1
+


Metabolite - 2053
1.35
1482.3
324.9
1
−


Metabolite - 2055
1.37
1502.0
269.9
1
+


Metabolite - 2056
1.37
1499.0
165.1
1
−


Metabolite - 2064
8.00
8312.0
193.2
1
+


Metabolite - 2072
1.57
1736.1
273.7
1
−


Metabolite - 2074
2.24
2380.9
280.1
1
+


Metabolite - 2075
2.71
2728.0
134.1
1
+


Metabolite - 2099
7.82
8135.9
469.2
1
+


Metabolite - 2100
1.33
1532.9
499
1
+


Metabolite - 2105
8.15
8442.0
433.6
1
+


Metabolite - 2108
8.76
8800.0
277.1
1
+


Metabolite - 2109
8.99
9266.0
321.1
1
+


Metabolite - 2111
9.19
9442.3
365.1
1
+


Metabolite - 2118
13.10
13367.8
547.1
1
+


Metabolite - 2121
14.18
14467.4
561.2
1
+


Metabolite - 2129
15.83
16363.2
526.3
1
+


Metabolite - 2130
16.28
16625.5
792.4
1
+


Metabolite - 2139
8.09
8500.0
218.1
1
+


Metabolite - 2141
9.39
9605.0
409.1
1
+


Metabolite - 2143
10.11
10327.0
585.1
1
+


Metabolite - 2150
13.27
13616.5
466.1
1
+


Metabolite - 2174
2.50
2569.0
250.1
1
+


Metabolite - 2175
3.84
4148.4
144
1
+


Metabolite - 2180
8.32
8663.0
490
1
+


Metabolite - 2181
8.37
8715.5
298
1
+


Metabolite - 2185
9.22
9499.4
246.2
1
+


Metabolite - 2194
13.65
13961.3
544.2
1
+


Metabolite - 2198
13.97
14284.8
530.1
1
+


Metabolite - 2212
15.96
16271.0
478.2
1
+


Metabolite - 2232
2.26
2318.0
754.8
1
−


Metabolite - 2237
10.14
10039.0
453.1
1
+


Metabolite - 2242
11.61
11926.0
254.3
1
+


Metabolite - 2249
14.21
14570.9
267.2
1
−


Metabolite - 2250
14.26
14668.4
286.3
1
+


Metabolite - 2254
1.53
1687.6
217.2
1
+


Metabolite - 2255 -
9.08
9394.0
539.1
1
+


hydroxyproline form of bradykinin


Metabolite - 2256
9.93
9867.0
460.8
1
+


Metabolite - 2259
11.25
11586.0
383.2
1
−


Metabolite - 2269
10.36
10727.0
255.1
1
−


Metabolite - 2271
12.95
13348.8
413.2
1
−


Metabolite - 2272
7.96
8377.0
189.1
1
−


Metabolite - 2277
10.07
10457.0
201.1
1
−


Metabolite - 2279
12.38
12781.0
490.1
1
+


Metabolite - 2281
13.93
14325.1
505.2
1
−


Metabolite - 2285
2.00
2146.0
699.6
1
−


Metabolite - 2287
12.95
13335.6
502.8
1
+


Metabolite - 2292
2.40
2900.0
343.9
1
−


Metabolite - 2293 - possible O-
8.86
9084.0
440.1
1
+


desmethylvenlafaxine


glucuronide


Metabolite - 2313
1.56
1685.6
352.9
1
−


Metabolite - 2316
8.82
9163.6
100.1
1
+


Metabolite - 2319
12.24
12626.0
367.2
1
−


Metabolite - 2323
7.55
7796.0
188.9
1
−


Metabolite - 2329
11.76
12177.6
541.2
1
−


Metabolite - 2347
13.65
14091.0
450.1
1
+


Metabolite - 2348
13.91
14293.5
448.3
1
+


Metabolite - 2366
8.47
8870.2
271
1
+


Metabolite - 2368
9.27
9615.5
573.2
1
−


Metabolite - 2370
16.13
16561.2
476.4
1
−


Metabolite - 2386
11.94
12320.3
539.2
1
−


Metabolite - 2387
8.55
9050.0
182.1
1
−


Metabolite - 2388
16.16
16900.0
259.1
1
−


Metabolite - 2389
1.49
1641.5
314.9
1
−


Metabolite - 2390
6.09
6410.0
517.4
1
+


Metabolite - 2391
10.14
10485.7
159.1
1
+


Metabolite - 2392
13.08
13460.4
379
1
−


Metabolite - 2406
14.69
15063.0
274.4
1
+


Metabolite - 2407
15.72
16127.6
637.3
1
+


Metabolite - 2466
9.19
8760.0
624.8
1
+


Metabolite - 2486
1.52
1667.0
635.7
1
−


Metabolite - 2506
14.05
14437.5
624.4
1
−


Metabolite - 2507
14.44
14843.0
481.4
1
−


Metabolite - 2546
1.63
1747.3
129.1
1
+


Metabolite - 2548 - possible Cl
5.97
6430.0
202.9
1
−


adduct of uric acid


Metabolite - 2550 - possible
11.09
11490.0
411.1
1
+


Riluzole glucuronide


Metabolite - 2557 - possible
11.79
11968.1
354.2
1
+


Pantoprazole metabolite


Metabolite - 2558 - possible N1-
8.14
8800.0
153.1
1
+


methyl-2-pyridone-5-carboxamide


and others


Metabolite - 2567
7.79
8464.7
247.1
1
+


Metabolite - 2591
9.99
10189.4
279.3
1
+


Metabolite - 2592
10.59
10600.0
697.4
1
−


Metabolite - 2607
10.01
10354.0
578.2
1
+


Metabolite - 2686
1.40
1593.0
219
1
−


Metabolite - 2688
1.42
1614.0
182
1
−


Metabolite - 2690
1.62
1786.2
441.1
1
+


Metabolite - 2691
1.69
1835.8
294.1
1
−


Metabolite - 2698
3.88
4500.0
157
1
+


Metabolite - 2703
8.86
9054.8
384.1
1
+


Metabolite - 2706
10.20
10428.3
247.2
1
+


Metabolite - 2711
2.22
2300.0
123
1
+


Metabolite - 2724
4.12
4499.3
206.1
1
+


Metabolite - 2726
8.30
8854.0
375.2
1
+


Metabolite - 2752
2.92
3200.0
189.1
1
+


Metabolite - 2753
3.38
3750.0
147
1
+


Metabolite - 2766
8.09
8395.0
397
1
+


Metabolite - 2768
9.13
9340.0
322.8
1
−


Metabolite - 2774
3.53
3796.0
230.9
1
+


Metabolite - 2778
7.97
8251.5
376.1
1
+


Metabolite - 2781
10.01
10224.6
202.2
1
−


Metabolite - 2806
1.38
1491.0
185.1
1
+


Metabolite - 2807
8.74
8920.3
380.8
1
+


Metabolite - 2809
8.74
8923.5
699.8
1
+


Metabolite - 2821
6.80
7680.0
119.1
1
+


Metabolite - 2824
12.72
12903.0
773.2
1
+


Metabolite - 2827
8.70
8877.0
419.5
1
+


Metabolite - 2846
9.19
9369.8
596.6
1
+


Metabolite - 2849 - related to
3.17
3375.0
482.6
1
−


citric acid?


Metabolite - 2853
8.74
8923.5
578.4
1
+


Metabolite - 2867
9.65
9908.0
235.3
1
+


Metabolite - 2888 - possible
9.87
10153.9
452
1
−


sulfated Rosiglitazone


Metabolite - 2893 - possible
9.99
10292.8
344.1
1
+


demethylated Rosiglitazone


Metabolite - 2897
10.96
10100.0
245.2
1
−


Metabolite - 2898
11.17
11463.3
213.1
1
−


Metabolite - 2900
13.35
13544.7
621.8
1
+


Metabolite - 2914
3.75
1096.1
214
Y
+


Metabolite - 2915
3.77
1099.0
174
Y
+


Metabolite - 2924 2-hydroxy
4.38
1170.7
130.9
Y
+


butanoic acid


Metabolite - 2973
4.74
1213.4
281
Y
+


Metabolite - 2974
4.76
1215.6
187
Y
+


Metabolite - 2978
5.01
1244.1
261.8
Y
+


Metabolite - 2981
5.21
1265.2
210.9
Y
+


Metabolite - 3002
6.74
1440.8
296.1
Y
+


Metabolite - 3003
6.79
1446.6
218.1
Y
+


Metabolite - 3004
6.81
1449.0
210.9
Y
+


Metabolite - 3012
7.17
1489.8
232
Y
+


Metabolite - 3014 - meso
7.43
1520.6
217.1
Y
+


erythritol


Metabolite - 3016
7.58
1537.5
186
Y
+


Metabolite - 3017
7.61
1541.4
246.1
Y
+


Metabolite - 3019
7.74
1556.4
260.1
Y
+


Metabolite - 3020
7.81
1564.1
292
Y
+


Metabolite - 3022
7.98
1584.9
142
Y
+


Metabolite - 3023
8.04
1590.9
274.1
Y
+


Metabolite - 3025
8.11
1600.3
274.1
Y
+


Metabolite - 3027
8.21
1610.6
142
Y
+


Metabolite - 3030
8.62
1659.7
320
Y
+


Metabolite - 3033
8.88
1689.4
116.9
Y
+


Metabolite - 3034
8.92
1694.9
299
Y
+


Metabolite - 3040
9.27
1735.7
274.1
Y
+


Metabolite - 3044
1.52
1615.3
150.1
1
+


Metabolite - 3051
8.69
8878.6
835.8
1
+


Metabolite - 3053
8.83
9042.0
170.2
1
+


Metabolite - 3055 - possible NH3
9.20
9443.0
196.8
1
+


adduct of hippuric acid


Metabolite - 3056
9.19
9432.0
185.2
1
+


Metabolite - 3058
9.70
1786.9
335.1
Y
+


Metabolite - 3064
13.80
13968.2
516.1
1
+


Metabolite - 3067
10.02
1824.2
132
Y
+


Metabolite - 3073
10.17
1838.8
362.1
Y
+


Metabolite - 3074
10.22
1844.5
204.1
Y
+


Metabolite - 3075
10.36
1857.9
204
Y
+


Metabolite - 3077
10.44
1866.2
308.1
Y
+


Metabolite - 3078
10.65
1887.0
203.1
Y
+


Metabolite - 3081
10.89
1911.5
204
Y
+


Metabolite - 3085 = Inositol 2
11.04
1926.1
217
Y
+


Metabolite - 3086
11.16
1938.5
221
Y
+


Metabolite - 3088
11.23
1946.1
372.2
Y
+


Metabolite - 3089
11.28
1951.5
116.9
Y
+


Metabolite - 3090
11.31
1955.0
243.1
Y
+


Metabolite - 3091
11.41
1966.2
232.1
Y
+


Metabolite - 3093
11.50
1975.6
204
Y
+


Metabolite - 3094
11.55
1980.6
299
Y
+


Metabolite - 3097
11.64
1990.4
204
Y
+


Metabolite - 3098
11.75
2003.0
308
Y
+


Metabolite - 3099
11.77
2005.2
204
Y
+


Metabolite - 3101
11.93
2022.2
290
Y
+


Metabolite - 3102
11.99
2028.2
217.1
Y
+


Metabolite - 3103
12.09
2039.8
290.1
Y
+


Metabolite - 3108
12.24
2056.5
246
Y
+


Metabolite - 3109
12.56
2092.6
202.1
Y
+


Metabolite - 3113
12.73
2113.5
406.2
Y
+


Metabolite - 3123
8.97
8763.0
334
1
+


Metabolite - 3125
11.88
12095.0
187.1
1
+


Metabolite - 3127
8.61
8812.0
260.1
1
−


Metabolite - 3129
8.80
9012.0
337.1
1
+


Metabolite - 3130
9.09
9328.0
158.2
1
+


Metabolite - 3131
10.49
10770.0
192.9
1
+


Metabolite - 3132
10.14
10177.0
260.2
1
+


Metabolite - 3134
14.33
14487.3
483.1
1
+


Metabolite - 3135
14.96
15107.7
467.2
1
+


Metabolite - 3138
8.63
8749.0
229.2
1
+


Metabolite - 3139
8.82
8934.5
176.1
1
+


Metabolite - 3143
9.81
10070.0
160.1
1
+


Metabolite - 3146
14.96
15105.0
499.1
1
−


Metabolite - 3160
12.11
12247.3
361
1
+


Metabolite - 3163 - possible
4.57
4837.5
258
1
+


methylcytidine, benserazide, Pyr-


Gln-OH, or


glycerophosphocholine


Metabolite - 3165
8.38
8472.2
265
1
+


Metabolite - 3166
8.69
8850.0
394.2
1
+


Metabolite - 3167
8.86
8929.0
197.1
1
+


Metabolite - 3169
9.27
9384.5
250
1
+


Metabolite - 3176 - possible
1.42
1750.0
132
1
+


creatine


Metabolite - 3178 - possible NH3
3.15
3670.0
210
1
+


adduct of isobar 42


Metabolite - 3180
4.14
4500.0
139
1
+


Metabolite - 3181
8.59
8621.4
165.1
1
+


Metabolite - 3183 - possible
9.37
9441.0
295.2
1
+


gamma-L-glutamyl-L-


phenylalanine


Metabolite - 3184
10.28
10364.4
223
1
+


Metabolite - 3189
12.06
12190.0
391
1
+


Metabolite - 3215
1.67
1733.8
173.8
1
+


Metabolite - 3216
1.68
1743.8
405.7
1
+


Metabolite - 3218
2.20
2257.0
148.1
1
+


Metabolite - 3220
3.73
4044.1
233.1
1
+


Metabolite - 3221
7.97
8050.0
204.1
1
+


Metabolite - 3231
3.08
3287.0
104.1
1
+


Metabolite - 3238
11.77
11827.4
220
1
+


Metabolite - 3243
11.34
11371.0
376.8
1
+


Metabolite - 3245
2.14
2168.3
816.7
1
−


Metabolite - 3246 - possible Ala-
4.73
5260.0
147.1
1
+


GLy, glycyl sarcosine, or ureido-


butyric acid


Metabolite - 3303
9.51
9799.5
170.1
1
+


Metabolite - 3309
8.37
8686.3
512.9
1
+


Metabolite - 3311
11.27
11597.0
308.2
1
+


Metabolite - 3313
8.10
8529.6
196.9
1
−


Metabolite - 3314
8.92
9143.5
264.8
1
+


Metabolite - 3317
8.42
8702.3
429.6
1
+


Metabolite - 3320 - possible
10.74
11300.0
245
1
−


pimpinellin or


tetrahydroxybenzophenone


Metabolite - 3322
11.82
12044.0
383.2
1
−


Metabolite - 3327
11.56
11784.0
385.3
1
−


Metabolite - 3364
9.06
9172.1
189
1
−


Metabolite - 3365
1.87
2068.3
115.1
1
+


Metabolite - 3370
8.11
8529.1
226.2
1
+


Metabolite - 3377
8.86
8963.9
270.2
1
+


Metabolite - 3379
1.51
1539.0
414.1
1
+


Metabolite - 3380
8.26
8602.1
164.1
1
+


Metabolite - 3381
2.31
2775.0
335
1
+


Metabolite - 3387
9.21
9377.5
463.1
1
+


Metabolite - 3390
8.14
8800.0
595.9
1
−


Metabolite - 3401
1.73
1863.3
131.1
1
+


Metabolite - 3402
8.90
8900.0
343.2
1
+


Metabolite - 3409
10.35
10636.4
259.1
1
+


Metabolite - 3426
10.71
11051.7
163
1
+


Metabolite - 3430 - possible gly-
2.78
3319.7
189.1
1
+


leu, acetyl-lys, ala-val


Metabolite - 3433
8.41
8681.7
327.1
1
−


Metabolite - 3436
8.91
9157.1
157
1
−


Metabolite - 3440
9.99
10317.6
252.8
1
−


Metabolite - 3441
1.51
1565.4
515
1
+


Metabolite - 3443
9.23
9420.6
194.8
1
−


Metabolite - 3457
3.81
4193.3
212.9
1
+


Metabolite - 3474
15.67
16524.3
228.3
1
+


Metabolite - 3475
1.66
1711.9
365.2
1
+


Metabolite - 3476
1.65
1709.7
377
1
−


Metabolite - 3484
13.59
13710.7
983.4
1
+


Metabolite - 3489
3.26
3840.0
226
1
+


Metabolite - 3493
9.57
9912.3
335.9
1
+


Metabolite - 3498
7.80
8368.7
279.1
1
+


Metabolite - 3507
10.01
10631.8
396.2
1
+


Metabolite - 3516
10.27
10895.1
411.3
1
+


Metabolite - 3517
10.27
10891.5
382.3
1
+


Metabolite - 3522
10.38
11005.0
362.3
1
+


Metabolite - 3526
10.42
11049.9
404.3
1
+


Metabolite - 3531
10.52
11400.0
384.3
1
+


Metabolite - 3534
10.54
11174.3
426.3
1
+


Metabolite - 3539
10.62
11259.8
435.2
1
+


Metabolite - 3543
10.67
11305.2
406.5
1
+


Metabolite - 3545
10.69
11331.3
448.4
1
+


Metabolite - 3554
10.91
11547.0
521.5
1
+


Metabolite - 3564
11.15
11792.0
471.7
1
+


Metabolite - 3576
1.38
1539.7
108
1
−


Metabolite - 3578
1.36
1525.2
296
1
+


Metabolite - 3603
8.41
8971.0
313.6
1
+


Metabolite - 3604
8.99
9551.9
214.2
1
−


Metabolite - 3605
9.59
10191.4
229.9
1
−


Metabolite - 3615
13.61
14343.6
868
1
+


Metabolite - 3624
10.36
10984.4
205.1
1
+


Metabolite - 3653 - Possible
4.05
4700.0
144.1
1
+


stachydrine


Metabolite - 3659
10.28
10447.6
427.2
1
+


Metabolite - 3660
10.32
10622.4
387.1
1
+


Metabolite - 3667
9.17
9120.0
301.1
1
+


Metabolite - 3668
9.63
9536.0
379.1
1
+


Metabolite - 3670
10.23
10459.0
213
1
−


Metabolite - 3694
8.05
8483.7
364.1
1
+


Metabolite - 3698
8.31
8640.2
273.1
1
+


Metabolite - 3701
1.34
1455.6
141.2
1
+


Metabolite - 3706
9.93
9717.0
348
1
+


Metabolite - 3707
13.07
13339.5
241
1
+


Metabolite - 3708
1.66
1625.3
159.9
1
+


Metabolite - 3752
8.61
8750.4
276.1
1
+


Metabolite - 3754
9.02
9152.5
190.2
1
+


Metabolite - 3755
9.81
9800.0
418.2
1
+


Metabolite - 3756
10.02
10319.0
160.9
1
+


Metabolite - 3758
12.44
12714.0
309.1
1
−


Metabolite - 3761
8.34
8750.0
212
1
+


Metabolite - 3765
9.22
9630.0
467.8
1
+


Metabolite - 3771
1.68
1761.0
227
1
−


Metabolite - 3772
2.22
2274.0
109
1
+


Metabolite - 3773
2.26
2275.3
153
1
+


Metabolite - 3778
7.37
7200.0
307.3
1
+


Metabolite - 3783
1.37
1464.0
271.1
1
+


Metabolite - 3786
10.19
9787.3
241.2
1
−


Metabolite - 3800
2.00
2400.0
255
1
−


Metabolite - 3802
2.18
2200.0
137.1
1
+


Metabolite - 3803
2.22
2435.0
198.1
1
+


Metabolite - 3804
2.44
2694.5
259
1
+


Metabolite - 3805
2.49
2600.0
229.1
1
+


Metabolite - 3806
2.80
3155.3
212.1
1
+


Metabolite - 3808
3.28
3719.0
288.8
1
−


Metabolite - 3810
3.74
4500.0
188.1
1
−


Metabolite - 3813
3.81
4312.0
212.1
1
+


Metabolite - 3816
4.16
5310.0
173.1
1
−


Metabolite - 3817
4.73
4701.0
143.1
1
+


Metabolite - 3824
7.88
8197.7
202.1
1
+


Metabolite - 3828
8.20
8495.7
245.2
1
+


Metabolite - 3830
8.42
8725.0
189
1
−


Metabolite - 3832 - possible
8.73
8995.8
173
1
−


phenol sulfate


Metabolite - 3833
8.81
9100.0
261.1
1
−


Metabolite - 3834 - Peptide
9.20
9285.0
372
1
+


Metabolite - 3837
9.26
9466.8
212.1
1
−


Metabolite - 3841
9.45
9638.0
245.1
1
−


Metabolite - 3843
9.54
9721.9
263.1
1
+


Metabolite - 3847
9.65
9816.6
206
1
+


Metabolite - 3848
9.73
9924.4
192
1
+


Metabolite - 3855
9.94
10142.0
243
1
−


Metabolite - 3873
9.94
10142.5
219.9
1
+


Metabolite - 3876
9.99
10195.0
273
1
−


Metabolite - 3877
10.02
10227.0
211
1
−


Metabolite - 3878
10.44
10673.0
245
1
+


Metabolite - 3879
11.07
11336.5
243
1
−


Metabolite - 3886
1.77
1903.3
255
1
−


Metabolite - 3887
2.33
2576.0
224.1
1
−


Metabolite - 3893
3.26
3724.5
409
1
+


Metabolite - 3896
3.38
3868.0
245.2
1
+


Metabolite - 3898
3.57
4100.0
194.9
1
+


Metabolite - 3900
4.53
4871.7
173.1
1
−


Metabolite - 3908
7.98
8301.7
150
1
+


Metabolite - 3909
8.21
8497.8
160.1
1
+


Metabolite - 3911
8.27
8568.2
116.1
1
+


Metabolite - 3951
8.41
8705.4
367.1
1
+


Metabolite - 3952
8.70
9150.0
297.2
1
+


Metabolite - 3955
8.68
8951.7
357.1
1
−


Metabolite - 3957
9.54
9720.8
159.3
1
−


Metabolite - 3960
8.49
8744.1
417.1
1
+


Metabolite - 3963
10.53
10787.0
652.1
1
+


Metabolite - 3966
11.53
11830.0
491.2
1
+


Metabolite - 3968
1.39
1436.0
327.8
1
+


Metabolite - 3970
4.52
4906.0
226
1
+


Metabolite - 3972
6.16
6304.0
432.6
1
−


Metabolite - 3973
9.57
9765.0
296.9
1
+


Metabolite - 3974
10.12
10349.0
604.1
1
+


Metabolite - 3977
11.03
11312.0
187.1
1
−


Metabolite - 3980
8.16
8480.4
353.1
1
+


Metabolite - 3981
10.01
10234.0
431
1
+


Metabolite - 3984
12.76
13134.0
489.1
1
+


Metabolite - 3986
13.12
13514.5
489.1
1
+


Metabolite - 3992 - possible Cl
1.40
1600.0
129.2
1
−


adduct of Formate dimer


Metabolite - 3994
1.63
1640.4
427
1
+


Metabolite - 3996
5.06
1236.0
176
Y
+


Metabolite - 3997
2.87
2876.0
564.9
1
−


Metabolite - 3998
5.22
1252.7
171
Y
+


Metabolite - 4002
5.69
1305.2
174
Y
+


Metabolite - 4003
3.94
4397.0
205
1
+


Metabolite - 4010
6.80
1432.8
218.1
Y
+


Metabolite - 4013
8.05
8399.5
547
1
−


Metabolite - 4014
7.17
1474.9
252
Y
+


Metabolite - 4015
7.37
1498.4
160
Y
+


Metabolite - 4017
7.62
1527.3
174
Y
+


Metabolite - 4018
8.35
8589.3
664
1
−


Metabolite - 4019
7.68
1534.5
174
Y
+


Metabolite - 4020
7.91
1561.5
220.1
Y
+


Metabolite - 4027
8.67
1650.2
274.1
Y
+


Metabolite - 4030 - possible
11.88
12214.7
218.1
1
+


glutethimide or securinine


Metabolite - 4031 - possible
14.26
14607.0
244.2
1
+


norlevorphenol,


isobutylphendienamide,


amprolium


Metabolite - 4032
8.95
1682.6
156.1
Y
+


Metabolite - 4042
10.23
1831.9
57.9
Y
+


Metabolite - 4043 lysine
10.29
1838.6
317.2
Y
+


Metabolite - 4046
10.80
1890.5
353.1
Y
+


Metabolite - 4051
11.56
1970.2
357.1
Y
+


Metabolite - 4053
11.87
2004.6
217.1
Y
+


Metabolite - 4058
12.46
2070.6
315.1
Y
+


Metabolite - 4075
13.27
2171.5
103
Y
+


Metabolite - 4078
16.49
16789.0
663.4
1
+


Metabolite - 4080
14.02
2270.2
299
Y
+


Metabolite - 4084
14.98
2393.9
441.3
Y
+


Metabolite - 4091 - possible
2.03
2084.7
277
1
+


gamma-glutamyl-glutamic acid


Metabolite - 4092
5.23
5668.0
256.1
1
+


Metabolite - 4096 - possible
8.60
8763.6
318.2
1
+


gamma-glu-gly-leu


Metabolite - 4112
8.46
8643.5
254.2
1
+


Metabolite - 4116
10.26
10582.0
272.2
1
+


Metabolite - 4117 - possible
14.70
15040.2
260.3
1
+


propranolol or 2-heptyl-3-


hydroxy-quinolone


Metabolite - 4133
4.35
1108.9
198
Y
+


Metabolite - 4134
5.51
1239.0
60.9
Y
+


Metabolite - 4147
10.07
1767.1
290.2
Y
+


Metabolite - 4148
10.23
1786.3
249.2
Y
+


Metabolite - 4150
11.34
1910.4
306.3
Y
+


Metabolite - 4163
1.35
1444.1
225.3
1
+


Metabolite - 4167
11.03
10920.4
286.2
1
+


Metabolite - 4168
13.69
13793.3
686.4
1
+


Metabolite - 4196
12.14
2000.4
290.2
Y
+


Metabolite - 4234
10.57
10467.0
564.4
1
+


Metabolite - 4235
10.91
10789.1
652.3
1
+


Metabolite - 4238
9.29
9192.0
828.5
1
+


Metabolite - 4251
4.09
1130.7
217
Y
+


Metabolite - 4271
9.69
1777.4
419.2
Y
+


Metabolite - 4272
10.28
1840.2
669.3
Y
+


Metabolite - 4274
10.37
1857.0
158.1
Y
+


Metabolite - 4275
10.68
1887.0
271.1
Y
+


Metabolite - 4331
13.95
14040.0
679
1
+


Metabolite - 4354
3.90
1074.3
110
Y
+


Metabolite - 4355
6.76
1396.9
102
Y
+


Metabolite - 4360
9.15
1678.2
347.2
Y
+


Metabolite - 4361
9.40
1706.2
232.2
Y
+


Metabolite - 4362
10.02
1779.9
319.2
Y
+


Metabolite - 4365
11.05
1892.9
204
Y
+


Metabolite - 4428
7.92
8236.5
229.2
1
+


Metabolite - 4448
9.54
9831.4
362.3
1
+


Metabolite - 4494
6.45
1363.2
221
Y
+


Metabolite - 4495
6.59
1381.0
117
Y
+


Metabolite - 4496
6.76
1398.2
204
Y
+


Metabolite - 4497
7.05
1431.6
218.1
Y
+


Metabolite - 4498
7.06
1434.9
103
Y
+


Metabolite - 4499
7.22
1453.0
189
Y
+


Metabolite - 4500
7.30
1460.7
172
Y
+


Metabolite - 4501 imino diacetic
7.96
1538.4
232.1
Y
+


acid


Metabolite - 4502
8.34
1581.3
273.1
Y
+


Metabolite - 4503
8.39
1589.0
227.2
Y
+


Metabolite - 4504
8.46
1597.1
244.1
Y
+


Metabolite - 4505
8.79
1633.4
285
Y
+


Metabolite - 4507
8.89
1644.9
245
Y
+


Metabolite - 4509
9.52
1720.6
204
Y
+


Metabolite - 4510
9.70
1740.1
254
Y
+


Metabolite - 4511
10.09
1788.4
206
Y
+


Metabolite - 4512
10.14
1790.7
345.1
Y
+


Metabolite - 4514
10.31
1812.3
342.2
Y
+


Metabolite - 4516
11.00
1886.5
217
Y
+


Metabolite - 4517
11.06
1892.7
217
Y
+


Metabolite - 4518
11.15
1902.4
295
Y
+


Metabolite - 4519
11.51
1941.8
193
Y
+


Metabolite - 4520
11.83
1978.1
325.1
Y
+


Metabolite - 4521
11.89
1983.4
383.1
Y
+


Metabolite - 4522
12.26
2025.4
217.1
Y
+


Metabolite - 4523
12.46
2047.0
258.1
Y
+


Metabolite - 4524
12.66
2071.3
210.1
Y
+


Metabolite - 4550
13.25
13286.2
568.2
1
+


Metabolite - 4567
3.50
3910.5
203.2
1
+


Metabolite - 4593
3.37
1011.1
170.9
Y
+


Metabolite - 4595
5.65
1274.4
130
Y
+


Metabolite - 4598
6.69
1392.2
169.9
Y
+


Metabolite - 4611
8.07
1546.6
292.1
Y
+


Metabolite - 4615
7.93
8250.0
222.1
1
+


Metabolite - 4617
8.39
8588.0
241.3
1
+


Metabolite - 4618
8.93
1651.1
349.2
Y
+


Metabolite - 4620
8.82
9001.0
312.1
1
+


Metabolite - 4624
10.01
1779.1
342.2
Y
+


Metabolite - 4628
10.11
1786.4
267.1
Y
+


Metabolite - 4629
10.29
1806.9
274.1
Y
+


Metabolite - 4632
10.59
1840.6
166
Y
+


Metabolite - 4633
10.69
1851.2
129
Y
+


Metabolite - 4634
11.00
1884.3
333.1
Y
+


Metabolite - 4635
11.19
1908.7
192.9
Y
+


Metabolite - 4636
11.50
1937.7
483.3
Y
+


Metabolite - 4637
11.95
1988.1
193
Y
+


Metabolite - 4638
12.25
2021.4
203.1
Y
+


Metabolite - 4639
12.87
2092.4
156.1
Y
+


Metabolite - 4649
5.33
5997.0
164.1
1
+


Metabolite - 4667
5.36
5652.8
320.1
1
−


Metabolite - 4706
8.92
9069.8
219
1
−


Metabolite - 4767
8.77
1626.2
116.9
Y
+


Metabolite - 4768
9.04
1661.7
279.1
Y
+


Metabolite - 4769
11.30
1916.4
156
Y
+


Metabolite - 4787
11.13
10895.5
289.4
1
+


Metabolite - 4791
10.29
1796.4
366.4
Y
+


Metabolite - 4795
14.83
2350.3
309
Y
+


Metabolite - 4796
3.53
1043.6
117
Y
+


Metabolite - 4806
4.20
1122.8
104.9
Y
+


Metabolite - 4866
9.18
9069.0
506.7
1
+


Metabolite - 4868 - confirmed
9.44
9356.0
531.2
1
+


Bradykinin


Metabolite - 4869
10.25
10112.8
534.5
1
+


Metabolite - 4931
1.50
1659.5
431
1
+


Metabolite - 4986
11.56
1956.4
204.1
Y
+


Metabolite - 5086
9.51
9738.3
388.2
1
+


Metabolite - 5087
9.69
9924.9
432.3
1
+


Metabolite - 5089
9.85
10075.9
476.3
1
+


Metabolite - 5107
11.87
11986.0
516.7
1
+


Metabolite - 5108
12.00
12116.5
538.7
1
+


Metabolite - 5109
12.12
12248.5
560.7
1
+


Metabolite - 5110
12.24
12350.5
582.6
1
+


Metabolite - 5126
9.78
10017.0
358.3
1
+


Metabolite - 5128
3.12
3462.8
558
1
−


Metabolite - 5147
8.21
8508.0
262.2
1
+


Metabolite - 5166
12.90
12999.4
491.5
1
+


Metabolite - 5167
12.97
13070.0
506.2
1
+


Metabolite - 5170
8.93
9156.3
279.1
1
+


Metabolite - 5186
1.55
1709.7
163.9
1
+


Metabolite - 5187
3.53
3985.5
489.1
1
+


Metabolite - 5189
16.33
16650.0
528.2
1
+


Metabolite - 5207
7.41
1493.6
151
Y
+


Metabolite - 5209
8.10
1573.6
218.2
Y
+


Metabolite - 5210
8.47
1616.4
254.1
Y
+


Metabolite - 5211
8.77
1652.1
326.2
Y
+


Metabolite - 5212
8.88
1665.1
306.1
Y
+


Metabolite - 5213
8.97
1675.3
111.1
Y
+


Metabolite - 5214
11.54
1960.0
117
Y
+


Metabolite - 5215
11.98
2008.0
163
Y
+


Metabolite - 5226
3.73
1073.9
102
Y
+


Metabolite - 5227
6.59
1398.6
151
Y
+


Metabolite - 5228
6.97
1442.5
181.1
Y
+


Metabolite - 5229
7.13
1461.6
211.1
Y
+


Metabolite - 5232
12.19
2031.5
134
Y
+


Metabolite - 5346
8.33
1573.0
202
Y
+


Metabolite - 5349
10.10
1782.2
312.1
Y
+


Metabolite - 5366
12.49
2044.7
204
Y
+


Metabolite - 5403
5.92
1300.2
319
Y
+


Metabolite - 5419
9.05
1664.1
349.2
Y
+


Metabolite - 5427
10.67
1853.0
192.9
Y
+


Metabolite - 5437
12.17
2017.4
204
Y
+


Metabolite - 5489
8.10
1550.3
247.1
Y
+


Metabolite - 5847
12.35
2040.0
288.2
Y
+


Metabolite - 5906
7.82
1541.2
313.9
Y
+


Metabolite - 5907
8.69
1643.2
229.1
Y
+









While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention.

## Claims

1. A method of diagnosing whether a subject has prostate cancer, comprising:
analyzing a prostate tissue sample from a subject to directly measure the levels of sarcosine and one or more additional biomarkers for prostate cancer in the sample, wherein the one or more additional biomarkers are selected from Tables 1 and 2, and
comparing the levels of sarcosine and the one or more additional biomarkers in the sample to prostate cancer-positive and/or prostate cancer-negative reference levels of sarcosine and the one or more additional biomarkers in order to diagnose whether the subject has prostate cancer, wherein an elevated level of sarcosine in the prostate tissue sample as compared to a prostate tissue sample from a subject not having prostate cancer is indicative that the subject has prostate cancer.

2. The method of claim 1, wherein the one or more additional biomarkers are selected from those biomarkers in Tables 1 and 2 having p values of less than 0.05 and/or those biomarkers in Tables 1 and 2 having q values of less than 0.10.

3. The method of claim 1, wherein the sample is analyzed using one or more techniques selected from the group consisting of gas chromatography, liquid chromatography, mass spectrometry, ELISA, and antibody linkage.

4. The method of claim 1, wherein the one or more additional biomarkers comprise one or more biomarkers selected from the group consisting of citric acid, spermine, and malic acid.

5. The method of claim 1, wherein the comparing step comprises comparing a ratio of a level of sarcosine and/or one or more additional biomarkers in Tables 1 and 2 having p values of less than 0.05 and/or those biomarkers in Tables 1 and 2 having q values of less than 0.10 to prostate cancer-positive and/or prostate cancer-negative reference levels in order to diagnose whether the subject has prostate cancer.

6. The method of claim 5, wherein the ratio of the level of one or more biomarkers comprises the level of a biomarker selected from the group consisting of sarcosine, spermine, and malic acid.

7. The method of claim 1, wherein the comparing step comprises comparing a ratio of the levels of sarcosine and/or one or more additional biomarkers to prostate cancer-positive and/or prostate cancer-negative reference levels in order to diagnose whether the subject has prostate cancer, wherein the ratio of levels is selected from the group consisting of the ratio of the levels of sarcosine and citric acid, sarcosine and spermine, and citric acid and malic acid.