# Patent

## Title
Identifying drugs for and diagnosis of benign prostatic hyperplasia using gene expression profiles

## Abstract

The present invention relates to a computer system comprising a database for elucidating changes in gene expression in prostate tissue isolated from patients exhibiting different clinical states of prostate hyperplasia as compared to normal prostate tissue, as well as the identification of individual genes that are differentially expressed in diseased prostate tissue.

## Background
RELATED APPLICATIONS
This application is a continuation-in-part of U.S. application Ser. No. 09/873,319, filed Jun. 5, 2001 now abandoned, which claims priority to U.S. Provisional Application No. 60/223,323, filed Aug. 7, 2000, both of which are herein incorporated by reference in their entirety.


BACKGROUND OF THE INVENTION
Benign Prostatic Hyperplasia (BPH) is the most common benign tumor in men aged >60 years. It is estimated that one in four men living to the age of 80 will require treatment for this disease. BPH is usually noted clinically after the age of 50, the incidence increasing with age, but as many as two thirds of men between the ages of 40 and 49 demonstrate histological evidence of the disease.
The anatomic location of the prostate at the bladder neck enveloping the urethra plays an important role in the pathology of BPH, including bladder outlet obstruction. Two prostate components are thought to play a role in bladder outlet obstruction. The first is the relative increased prostate tissue mass. The second component is the prostatic smooth muscle tone.
The causative factors of BPH in man have been intensively studied. See Ziada et al., Urology, 53: 1-6, 1999. In general, the two most important factors appear to be aging and the presence of functional testes. Although these factors appear to be key to the development of BPH, both appear to be nonspecific.
Little is known about the molecular changes in prostate cells associated with the development and progression of BPH. It has been demonstrated that the expression levels of a number of individual genes are changed compared to normal prostate cells. These changes in gene expression include decreased expression of Wilm's tumor gene (WT-1) and increased expression of insulin growth factor II (IGF-II) (Dong et al., J. Clin. Endocrin. Metab., 82(7): 2198-220).
While the changes in the expression levels of a number of individual genes have been identified, the investigation of the global changes in gene expression has not been reported. Accordingly, there exists a need for the investigation of the changes in global gene expression levels as well as the need for the identification of new molecular markers associated with the development and progression of BPH. Furthermore, if intervention is expected to be successful in halting or slowing down BPH, means of accurately assessing the early manifestations of BPH need to be established. One way to accurately assess the early manifestations of BPH is to identify markers which are uniquely associated with disease progression. Likewise, the development of therapeutics to prevent or stop the progression of BPH relies on the identification of genes responsible for BPH growth and function.
SUMMARY OF THE INVENTION
The present invention is based on the elucidation of the global changes in gene expression in BPH tissue isolated from patients exhibiting different clinical states of prostate hyperplasia as compared to normal prostate tissue as well as the identification of individual genes that are differentially expressed in BPH tissue.
The invention is also based on the discovery of a means of effectively selecting disease-linked drug targets from gene expression results. The invention includes methods of classifying genes whose expression levels are changed in diseased tissues, during disease induction or during disease progression into specific groups. By using this method it is possible to classify genes whose expression are regulated by the same mechanism into the same group, and it is possible to identify representative marker genes by selecting typical genes from each cluster.
The invention includes methods of screening for or identifying an agent that modulates the onset or progression of BPH, comprising: preparing a first gene expression profile of BPH cells; exposing the cells to the agent; preparing a second gene expression profile of the agent exposed cells; and comparing the first and second gene expression profiles. In a preferred embodiment of these methods, the gene expression profile comprises the expression levels of one or more or preferably two or more genes in Tables 1-6. In another preferred embodiment of these methods, the cell is a prostate cell from a BPH patient, a cell line in Table 7, or a derivative thereof.
The invention also includes methods of monitoring a treatment of a patient with BPH, comprising administering a pharmaceutical composition to the patient; preparing a gene expression profile from a prostate cell or tissue sample from the patient; and comparing the patient gene expression profile to a gene expression profile from a normal prostate cell population, a BPH tissue or BPH cells without treatment with the pharmaceutical composition. In preferred embodiments of these methods, the gene expression profile comprises the expression levels of one or more or, preferably two or more genes in Tables 1-6.
The invention also includes methods of diagnosing benign prostatic hyperplasia (BPH) in a subject comprising the step of detecting the level of expression in a tissue or cell sample from the subject of two or more genes from Tables 1-6 (preferably Tables 3-5, and more preferably Table 5); wherein differential expression of the genes is indicative of BPH progression.
The invention further includes methods of detecting the onset or progression of benign prostatic hyperplasia (BPH) in a patient comprising the step of detecting the level of expression in a tissue or cell sample of two or more genes from Tables 1-6 (preferably Tables 3-5, and more preferably Table 5); wherein differential expression of the genes is indicative of BPH progression.
The invention also includes methods of differentiating benign prostatic hyperplasia (BPH) from prostate cancer in a patient comprising the step of detecting the level of expression in a tissue or cell sample of two or more genes from Tables 1-6 (preferably Tables 3-5, and more preferably Table 5); wherein differential expression of the genes is indicative of BPH rather than prostate cancer.
The invention also includes methods of selecting or identifying cells that can be used for drug screening.
All of these methods may include the step of detecting the expression levels of at least about 2, 3, 4, 5, 6, 7, 8, 9, 10 or more genes in any of Tables 1-6, or preferably Table 5. In a preferred embodiment, expression of all of the genes or nearly all of the genes in Tables 1-6, or preferably Table 5, may be detected.
The invention further includes sets of at least two or more probes, wherein each of the probes comprises a sequence that specifically hybridizes to a gene in Tables 1-6 as well as solid supports comprising at least two or more of the probes.
The invention also includes computer systems comprising or linked to a database containing information identifying the expression level in BPH tissue or cells of a set of genes comprising at least two genes in Tables 1-6, preferably from Table 5; and a user interface to view the information. The database may further comprise sequence information for the genes as well as information identifying the expression level for the set of genes in normal prostate tissue or cells, and prostate cancer tissue. The database may further contain or be linked to descriptive information from an external database, which information correlates said genes to records in the external database.
The invention further includes methods of using the disclosed computer systems to present information identifying the expression level in a tissue or cell of a set of genes comprising at least one of the genes in Tables 1-6, preferably Table 5, comprising comparing the expression level of at least one gene in Tables 1-6, preferably Table 5, in the tissue or cell to the level of expression of the gene in the database.
Lastly, the invention includes kits comprising probes or solid supports of the invention. In some embodiments, the kits also contain written materials or software concerning gene expression information for the genes of the invention, preferably in electronic format.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1. FIG. 1 shows the expression of cellular retinol binding protein RNA in various tissues.
FIG. 2. FIG. 2 shows the expression of cellular retinol binding protein RNA in various prostate tissues samples. In all of the figures, “Normal”, “−Sym”, “Cancer” and “+Sym” refer to normal prostate, BPH without symptoms, prostate cancer, and BPH with symptoms, respectively.
FIG. 3. FIG. 3 shows the expression of S100 calcium binding protein RNA in various tissues.
FIG. 4. FIG. 4 shows the expression of S100 calcium binding protein RNA in various prostate tissue samples.
FIG. 5. FIG. 5 shows the expression of human prostate-specific membrane antigen (PSMA) RNA in various tissues.
FIG. 6. FIG. 6 shows the expression of PSMA RNA in various prostate tissue samples.
FIGS. 7A-7C. FIG. 7A shows a 3-dimensional view of the results of a Preferred Component Analysis (PCA) comparing BPH patients with symptoms (S), asymptomatic BPH patients (O), asymptomatic BPH patients with prostate cancer (C) and normal control subjects (N). FIG. 7B shows the same PCA in a 2-dimensional format plotting component 1 versus components 2+3. The patients are depicted here as: BPH patients with symptoms (BPHWS), asymptomatic BPH patients (BPHNoS), asymptomatic BPH patients with prostate cancer (Cancer) and normal control subjects (Normal). FIG. 7C depicts the same data as FIG. 7B, with the addition of two additional normal (Norm) and three additional BPH patients with symptoms (BPH).



DETAILED DESCRIPTION
Many biological functions are accomplished by altering the expression of various genes through transcriptional (e.g. through control of initiation, provision of RNA precursors, RNA processing, etc.) and/or translational control. For example, fundamental biological processes such as cell cycle, cell differentiation and cell death, are often characterized by the variations in the expression levels of groups of genes.
Changes in gene expression also are associated with pathogenesis. For example, the lack of sufficient expression of functional tumor suppressor genes and/or the over expression of oncogene/protooncogenes could lead to tumorgenesis or hyperplastic growth of cells (Marshall, Cell, 64: 313-326 (1991); Weinberg, Science, 254:1138-1146 (1991)). Thus, changes in the expression levels of particular genes (e.g. oncogenes or tumor suppressors) serve as signposts for the presence and progression of various diseases.
Monitoring changes in gene expression may also provide certain advantages during drug screening development. Often drugs are screened for the ability to interact with a major target without regard to other effects the drugs have on cells. Often such other effects cause toxicity in the whole animal, which prevent the development and use of the potential drug.
The present inventors have examined tissue from normal prostate, BPH and BPH prostate tissue immediately adjacent to malignant prostate tissue to identify the global changes in gene expression in BPH. These changes in gene expression, also referred to as expression profiles, provide useful markers for diagnostic uses as well as markers that can be used to monitor disease states, disease progression, toxicity, drug efficacy and drug metabolism.
Assay Formats
The genes identified as being differentially expressed in BPH tissue or BPH cells (Tables 1-6) may be used in a variety of nucleic acid detection assays to detect or quantititate the expression level of a gene or multiple genes in a given sample. For example, traditional Northern blotting, nuclease protection, RT-PCR and differential display methods may be used for detecting gene expression levels. Those methods are useful for some embodiments of the invention, particularly when smaller numbers of genes are assayed. For instance, when fewer than 50 genes are assayed, RT-PCR techniques can be used to prepare high-throughput assays. However, methods and assays of the invention are most efficiently designed with hybridization-based methods for detecting the expression of a large number of genes.
Any hybridization assay format may be used, including solution-based and solid support-based assay formats. Solid supports containing oligonucleotide probes for differentially expressed genes of the invention can be filters, polyvinyl chloride dishes, silicon or glass based beads or chips, etc. Such supports and hybridization methods are widely available, for example, those disclosed by Beattie (WO 95/11755). Any solid surface to which oligonucleotides can be bound, either directly or indirectly, either covalently or non-covalently, can be used.
A preferred solid support is a high density array or DNA chip. These contain a particular oligonucleotide probe in a predetermined location on the array. Each predetermined location may contain more than one molecule of the probe, but each molecule within the predetermined location has an identical sequence. Such predetermined locations are termed features. There may be, for example, from 2, 10, 100, 1000 to 10,000, 100,000 or 400,000 of such features on a single solid support. The solid support, or the area within which the probes are attached may be on the order of about a square centimeter.
Oligonucleotide probe arrays for expression monitoring can be made and used according to any technique known in the art (see for example, Lockhart et al., Nat. Biotechnol. (1996) 14, 1675-1680; McGall et al., Proc. Nat. Acad. Sci. USA (1996) 93, 13555-13460). Such probe arrays may contain at least two or more oligonucleotides that are complementary to or hybridize to two or more of the genes described in Tables 1-6. For instance, such arrays may contain oligonucleotides that are complementary or hybridize to at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 50, 70 or more of the genes described herein.
The genes which are assayed according to the present invention are typically in the form of mRNA or reverse transcribed mRNA. The genes may be cloned or not. The genes may be amplified or not. The cloning itself does not appear to bias the representation of genes within a population. However, it may be preferable to use polyA+ RNA as a source, as it can be used with less processing steps.
The sequences and related information of the genes described herein are available in the public databases. Tables 1-6 provide the Accession numbers and name for each of the sequences. Each Accession Number corresponds to a sequence in the attached sequence listing. The sequences and related information of the genes listed in the Tables according to their GenBank identifiers are expressly incorporated herein as of the filing date of this application, as are sequences in the databases related to those herein described, such as fragments, variant sequences, etc.
Probes based on the sequences of the genes described above may be prepared by any commonly available method. Oligonucleotide probes for interrogating the tissue or cell sample are preferably of sufficient length to specifically hybridize only to appropriate, complementary genes or transcripts. Typically the oligonucleotide probes will be at least 10, 12, 14, 16, 18, 20 or 25 nucleotides in length. In some cases longer probes of at least 30, 40, or 50 nucleotides will be desirable.
As used herein, oligonueleotide sequences that are complementary to one or more of the genes described in Tables 1-6 refer to oligonucleotides that are capable of hybridizing under stringent conditions to at least part of the nucleotide sequence of said genes. Such hybridizable oligonucleotides will typically exhibit at least about 75% sequence identity at the nucleotide level to said genes, preferably about 80% or 85% sequence identity or more preferably about 90% or 95% or more sequence identity to said genes.
“Bind(s) substantially” refers to complementary hybridization between a probe nucleic acid and a target nucleic acid and embraces minor mismatches that can be accommodated by reducing the stringency of the hybridization media to achieve the desired detection of the target polynucleotide sequence.
The terms “background” or “background signal intensity” refer to hybridization signals resulting from non-specific binding, or other interactions, between the labeled target nucleic acids and components of the oligonucleotide array (e.g., the oligonucleotide probes, control probes, the array substrate, etc.). Background signals may also be produced by intrinsic fluorescence of the array components themselves. A single background signal can be calculated for the entire array, or a different background signal may be calculated for each target nucleic acid. In a preferred embodiment, background is calculated as the average hybridization signal intensity for the lowest 5% to 10% of the probes in the array, or, where a different background signal is calculated for each target gene, for the lowest 5% to 10% of the probes for each gene. Of course, one of skill in the art will appreciate that where the probes to a particular gene hybridize well and thus appear to be specifically binding to a target sequence, they should not be used in a background signal calculation. Alternatively, background may be calculated as the average hybridization signal intensity produced by hybridization to probes that are not complementary to any sequence found in the sample (e.g. probes directed to nucleic acids of the opposite sense or to genes not found in the sample such as bacterial genes where the sample is mammalian nucleic acids). Background can also be calculated as the average signal intensity produced by regions of the array that lack probes.
The phrase “hybridizing specifically to” refers to the binding, duplexing, or hybridizing of a molecule substantially to or only to a particular nucleotide sequence or sequences under stringent conditions when that sequence is present in a complex mixture (e.g., total cellular DNA or RNA).
Assays and methods of the invention may utilize available formats to simultaneously screen at least about 100, preferably about 1000, more preferably about 10,000 and most preferably about 1,000,000 different nucleic acid hybridizations.
As used herein a “probe” is defined as a nucleic acid molecule, capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation. As used herein, a probe may include natural (i.e., A, G, U, C, or T) or modified bases (7-deazaguanosine, inosine, etc.). In addition, the bases in probes may be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization. Thus, probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.
The term “stringent conditions” refers to conditions under which a probe will hybridize to its target subsequence, but with only insubstantial hybridization to other sequences or to other sequences such that the difference may be identified. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH.
Typically, stringent conditions will be those in which the salt concentration is at least about 0.01 to 1.0 M Na ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes (e.g., 10 to 50 nucleotide). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide.
The “percentage of sequence identity” or “sequence identity” is determined by comparing two optimally aligned sequences or subsequences over a comparison window or span, wherein the portion of the polynucleotide sequence in the comparison window may optionally comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences.
The percentage is calculated by determining the number of positions at which the identical submit (e.g. nucleic acid base or amino acid residue) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity. Percentage sequence identity when calculated using the programs GAP or BESTFIT (see below) is calculated using default gap weights.
Probe Design
One of skill in the art will appreciate that an enormous number of array designs are suitable for the practice of this invention. The high density array will typically include a number of probes that specifically hybridize to the sequences of interest. See WO 99/32660 for methods of producing probes for a given gene or genes. In addition, in a preferred embodiment, the array will include one or more control probes.
High density array chips of the invention include “test probes.” Test probes could be oligonucleotides that range from about 5 to about 500 or 5 to about 45 nucleotides, more preferably from about 10 to about 40 nucleotides and most preferably from about 15 to about 40 nucleotides in length. In other particularly preferred embodiments the probes are 20 or 25 nucleotides in length. In another preferred embodiment, test probes are double or single strand DNA sequences. DNA sequences are isolated or cloned from natural sources or amplified from natural sources using native nucleic acid as templates. These probes have sequences complementary to particular subsequences of the genes whose expression they are designed to detect. Thus, the test probes are capable of specifically hybridizing to the target nucleic acid they are to detect (the genes of Tables 1-6).
The term “perfect match probe” refers to a probe that has a sequence that is perfectly complementary to a particular target sequence. The probe is typically perfectly complementary to a portion (subsequence) of the target sequence. The perfect match (PM) probe can be a “test probe”, a “normalization control” probe, an expression level control probe and the like. A perfect match control or perfect match probe is, however, distinguished from a “mismatch control” or “mismatch probe.”
In addition to test probes that bind the target nucleic acid(s) of interest, the high density array can contain a number of control probes. The control probes fall into three categories referred to herein as 1) normalization controls; 2) expression level controls; and 3) mismatch controls.
Normalization controls are oligonucleotide or other nucleic acid probes that are complementary to labeled reference oligonucleotides or other nucleic acid sequences that are added to the nucleic acid sample to be screened. The signals obtained from the normalization controls after hybridization provide a control for variations in hybridization conditions, label intensity, “reading” efficiency and other factors that may cause the signal of a perfect hybridization to vary between arrays. In a preferred embodiment, signals (e.g., fluorescence intensity) read from all other probes in the array are divided by the signal (e.g., fluorescence intensity) from the control probes thereby normalizing the measurements.
Virtually any probe may serve as a normalization control. However, it is recognized that hybridization efficiency varies with base composition and probe length. Preferred normalization probes are selected to reflect the average length of the other probes present in the array, however, they can be selected to cover a range of lengths. The normalization control(s) can also be selected to reflect the (average) base composition of the other probes in the array, however in a preferred embodiment, only one or a few probes are used and they are selected such that they hybridize well (i.e., no secondary structure) and do not match any target-specific probes.
Expression level controls are probes that hybridize specifically with constitutively expressed genes in the biological sample. Virtually any constitutively expressed gene provides a suitable target for expression level controls. Typically expression level control probes have sequences complementary to subsequences of constitutively expressed “housekeeping genes” including, but not limited to an actin gene, the transferrin receptor gene, the GAPDH gene, and the like.
Mismatch controls or mismatch probes may also be provided for the probes to the target genes, for expression level controls or for normalization controls. Mismatch controls are oligonucleotide probes or other nucleic acid probes identical to their corresponding test or control probes except for the presence of one or more mismatched bases. A mismatched base is a base selected so that it is not complementary to the corresponding base in the target sequence to which the probe would otherwise specifically hybridize. One or more mismatches are selected such that under appropriate hybridization conditions (e.g., stringent conditions) the test or control probe would be expected to hybridize with its target sequence, but the mismatch probe would not hybridize (or would hybridize to a significantly lesser extent). Preferred mismatch probes contain a central mismatch. Thus, for example, where a probe is a 20 mer, a corresponding mismatch probe will have the identical sequence except for a single base mismatch (e.g., substituting a G, a C or a T for an A) at any of positions 6 through 14 (the central mismatch).
Mismatch probes thus provide a control for non-specific binding or cross hybridization to a nucleic acid in the sample other than the target to which the probe is directed. Mismatch probes also indicate whether a hybridization is specific or not. For example, if the target is present the perfect match probes should be consistently brighter than the mismatch probes. In addition, if all central mismatches are present, the mismatch probes can be used to detect a mutation. The difference in intensity between the perfect match and the mismatch probe provides a good measure of the concentration of the hybridized material.
Nucleic Acid Samples
As is apparent to one of ordinary skill in the art, nucleic acid samples used in the methods and assays of the invention may be prepared by any available method or process. Methods of isolating total mRNA are well known to those of skill in the art. For example, methods of isolation and purification of nucleic acids are described in detail in Chapter 3 of Laboratory Techniques in Biochemistry and Molecular Biology: Hybridization With Nucleic Acid Probes, Part I Theory and Nucleic Acid Preparation, P. Tijssen, Ed., Elsevier, N.Y. (1993). Such samples include RNA samples, but also include cDNA synthesized from a mRNA sample isolated from a cell or tissue of interest. Such samples also include DNA amplified from the cDNA, and RNA transcribed from the amplified DNA. One of skill in the art would appreciate that it is desirable to inhibit or destroy RNase present in homogenates before homogenates can be used.
Biological samples may be of any biological tissue or fluid or cells from any organism as well as cells raised in vitro, such as cell lines and tissue culture cells. Biological samples may also include sections of tissues, such as frozen sections or formalin fixed sections taken for histological purposes. Frequently, the sample will be a “clinical sample” which is a sample derived from a patient. Typical clinical samples include, but are not limited to prostate tissue, urine, sputum, blood, blood-cells (e.g., white cells or peripheral blood leukocytes (PBL), tissue or fine needle biopsy samples, peritoneal fluid, and pleural fluid, or cells therefrom.
Forming High Density Arrays
Methods of forming high density arrays of oligonucleotides with a minimal number of synthetic steps are known. The oligonucleotide analogue array can be synthesized on a solid substrate by a variety of methods, including, but not limited to, light-directed chemical coupling, and mechanically directed coupling. See Pirrung et al., U.S. Pat. No. 5,143,854.
In brief, the light-directed combinatorial synthesis of oligonucleotide arrays on a glass surface proceeds using automated phosphoramidite chemistry and chip masking techniques. In one specific implementation, a glass surface is derivatized with a silane reagent containing a functional group, e.g., a hydroxyl or amine group blocked by a photolabile protecting group. Photolysis through a photolithogaphic mask is used selectively to expose functional groups which are then ready to react with incoming 5′ photoprotected nucleoside phosphoramidites. The phosphoramidites react only with those sites which are illuminated (and thus exposed by removal of the photolabile blocking group). Thus, the phosphoramidites only add to those areas selectively exposed from the preceding step. These steps are repeated until the desired array of sequences have been synthesized on the solid surface. Combinatorial synthesis of different oligonucleotide analogues at different locations on the array is determined by the pattern of illumination during synthesis and the order of addition of coupling reagents.
In addition to the foregoing, additional methods which can be used to generate an array of oligonucleotides on a single substrate are described in WO 93/09668. High density nucleic acid arrays can also be fabricated by depositing premade or natural nucleic acids in predetermined positions. Synthesized or natural nucleic acids are deposited on specific locations of a substrate by light directed targeting and oligonucleotide directed targeting. Another embodiment uses a dispenser that moves from region to region to deposit nucleic acids in specific spots.
Hybridization
Nucleic acid hybridization simply involves contacting a probe and target nucleic acid under conditions where the probe and its complementary target can form stable hybrid duplexes through complementary base pairing. See WO 99/32660. The nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, typically through detection of an attached detectable label. It is generally recognized that nucleic acids are denatured by increasing the temperature or decreasing the salt concentration of the buffer containing the nucleic acids. Under low stringency conditions (e.g., low temperature and/or high salt) hybrid duplexes (e.g., DNA:DNA, RNA:RNA, or RNA:DNA) will form even where the annealed sequences are not perfectly complementary.
Thus specificity of hybridization is reduced at lower stringency. Conversely, at higher stringency (e.g., higher temperature or lower salt) successful hybridization tolerates fewer mismatches. One of skill in the art will appreciate that hybridization conditions may be selected to provide any degree of stringency. In a preferred embodiment, hybridization is performed at low stringency in this case in 6× SSPE-T at 37° C. (0.005% Triton X-100) to ensure hybridization and then subsequent washes are performed at higher stringency (e.g., I× SSPE-T at 37° C.) to eliminate mismatched hybrid duplexes. Successive washes may be performed at increasingly higher stringency (e.g., down to as low as 0.25× SSPET at 37° C. to 50° C.) until a desired level of hybridization specificity is obtained. Stringency can also be increased by addition of agents such as formamide. Hybridization specificity may be evaluated by comparison of hybridization to the test probes with hybridization to the various controls that can be present (e.g., expression level control, normalization control, mismatch controls, etc.).
In general, there is a tradeoff between hybridization specificity (stringency) and signal intensity. Thus, in a preferred embodiment, the wash is performed at the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity. Thus, in a preferred embodiment, the hybridized array may be washed at successively higher stringency solutions and read between each wash. Analysis of the data sets thus produced will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest.
Signal Detection
The hybridized nucleic acids are typically detected by detecting one or more labels attached to the sample nucleic acids. The labels may be incorporated by any of a number of means well known to those of skill in the art. See WO 99/32660.
Databases
The present invention includes relational databases containing sequence information, for instance for the genes of Tables 1-6, as well as gene expression information in various prostate tissue samples. Databases may also contain information associated with a given sequence or tissue sample such as descriptive information about the gene associated with the sequence information, metabolic pathway information for the gene or descriptive information concerning the clinical status of the tissue sample, or the patient from which the sample was derived. Such information for the patient may include, but is not limited to sex, age, disease status, general health information, surgical or treatment status, PSA levels, as well as information concerning the patient's clinical symptoms. The database may be designed to include different parts, for instance a sequence database and a gene expression database. Methods for the configuration and construction of such databases are widely available, for instance, see U.S. Pat. No. 5,953,727, which is herein incorporated by reference in its entirety.
The databases of the invention may be linked to an outside or external database. In a preferred embodiment, as described in Tables 1-6, the external database is GenBank and the associated databases maintained by the National Center for Biotechnology Information (NCBI).
Any appropriate computer platform may be used to perform the necessary comparisons between sequence information, gene expression information and any other information in the database or provided as an input. For example, a large number of computer workstations are available from a variety of manufacturers, such has those available from Silicon Graphics. Client/server environments, database servers and networks are also widely available and appropriate platforms for the databases of the invention.
The databases of the invention may be used to produce, among other things, electronic Northerns that allow the user to determine the cell type or tissue in which a given gene is expressed and to allow determination of the abundance or expression level of a given gene in a particular tissue or cell.
The databases of the invention may also be used to present information identifying the expression level in a tissue or cell of a set of genes comprising at least two of the genes in Tables 1-6, comprising the step of comparing the expression level of at least one gene in Tables 1-6 found or detected in the tissue to the level of expression of the gene in the database. Such methods may be used to predict the hyperplastic state of a given tissue by comparing the level of expression of a gene or genes in Tables 1-6 from a sample to the expression levels found in normal prostate cells, BPH cells or tissue and/or malignant or cancerous prostate tissue. Such methods may also be used in the drug or agent screening assays as described below.
Selection of BPH-Associated Genes
BPH associated genes may be identified or selected by any available method, including subtractive hybridization protocols, differential display protocols and high-throughput hybridization formats, including oligonucleotide and cDNA microarray technologies.
Unprocessed or raw expression levels may be normalized, standardized and/or analyzed by any available computational method, including the expression level normalization, analysis and clustering methods herein described. The normalization method as described in Example 4 may be combined with any further analysis method, including any clustering methods available in the art.
Diagnostic Uses for the BPH Markers
As described above, the genes and gene expression information provided in Tables 1-1s 6 may be used as diagnostic markers for the prediction or identification of the hyperplastic state of a prostate or other tissue. For instance, a prostate tissue or other patient sample may be assayed by any of the methods described above, and the expression levels from a gene or genes from Tables 1-6 may be compared to the expression levels found in normal prostate tissue, BPH tissue or BPH tissue from a patient with metastatic or nonmetastatic prostate cancer. In some instances, patient PBLs may be used as the patient sample. The comparison of expression data, as well as available sequence or other information may be done by researcher or diagnostician or may be done with the aid of a computer and databases as described above.
Use of the BPH Markers for Monitoring Disease Progression
As described above, the genes and gene expression information provided in Tables 1-6 may also be used as markers for the monitoring of disease progression, such as the development of BPH. For instance, a prostate tissue or other patient sample may be assayed by any of the methods described above, and the expression levels from a gene or genes from Tables 1-6 may be compared to the expression levels found in normal prostate tissue, BPH tissue or BPH tissue from a patient with metastatic or nonmetastatic prostate cancer. The comparison of the expression data, as well as available sequence or other information may be done by researcher or diagnostician or may be done with the aid of a computer and databases as described above.
The BPH markers of the invention may also be used to track or predict the progress or efficacy of a treatment regime in a patient. For instance, a patient's progress or response to a given drug may be monitored by creating a gene expression profile from a tissue or cell sample after treatment or administration of the drug. The gene expression profile may then be compared to a gene expression profile prepared from normal cells or tissue, for instance, normal prostate tissue. The gene expression profile may also be compared to a gene expression profile prepared from BPH or malignant prostate cells, or from tissue or cells from the same patient before treatment. The gene expression profile may be made from at least one gene, preferably more than one gene, and most preferably all or nearly all of the genes in Tables 1-6.
Use of the BPH Markers for Drug Screening
According to the present invention, the genes identified in Tables 1-6 can be used as markers to screen for potential therapeutic agents or compounds to treat BPH or prostate cancer. A candidate drug or agent can be screened for the ability to stimulate the transcription or expression of a given marker or to down-regulate or counteract the transcription or expression of a marker or markers. Compounds that modulate the expression level of single gene and also compounds that modulate the expression level of multiple genes from levels associated with a specific disease state to a normal state can be screened by using the markers and profiles identified herein.
According to the present invention, one can also compare the specificity of drug's effects by looking at the number of markers which are differentially expressed after drug exposure and comparing them. More specific drugs will have less transcriptional targets. Similar sets of markers identified for two drugs may indicate a similarity of effects.
Assays to monitor the expression of a marker or markers as defined in Tables 1-6 may utilize any available means of monitoring for changes in the expression level of the nucleic acids of the invention. As used herein, an agent is said to modulate the expression of a nucleic acid of the invention if it is capable of up- or down-regulating expression of the nucleic acid in a cell.
In one assay format, gene chips containing probes to at least 2 genes from Tables 1-6 may be used to directly monitor or detect changes in gene expression in the treated or exposed cell as described in more detail above. In another format, the changes of mRNA expression level can be detected using QuantiGene technology (Warrior et. al. (2000) J. Biomolecular Screening, 5, 343-351). Specific probes used for QuantiGene can be designed and synthesized to one or more genes from Tables 1-6. Cells treated with compounds are lysed by lysis buffer. The amount of target mRNA can be detected as a luminescence intensity using target specific probes.
In another format, cell lines that contain reporter gene fusions between the open reading frame and/or 5′/3′ regulatory regions of a gene in Tables 1-6 and any assayable fusion partner may be prepared. Numerous assayable fusion partners are known and readily available including the firefly luciferase gene and the gene encoding chloramphenicol acetyltransferase (Alam et al. (1990) Anal. Biochem. 188:245-254). Cell lines containing the reporter gene fusions are then exposed to the agent to be tested under appropriate conditions and time. Differential expression of the reporter gene between samples exposed to the agent and control samples identifies agents which modulate the expression of the nucleic acid.
Additional assay formats may be used to monitor the ability of the agent to modulate the expression of a gene identified in Tables 1-6. For instance, as described above, mRNA expression may be monitored directly by hybridization of probes to the nucleic acids of the invention. Cell lines are exposed to the agent to be tested under appropriate conditions and time and total RNA or mRNA is isolated by standard procedures such those disclosed in Sambrook et al. (Molecular Cloning: A Laboratory Manual, 2nd Ed. Cold Spring Harbor Laboratory Press, 1989).
In another assay format, cells or cell lines are first identified which express the gene products of the invention physiologically (see below). Cell and/or cell lines so identified would be expected to comprise the necessary cellular machinery such that the fidelity of modulation of the transcriptional apparatus is maintained with regard to exogenous contact of agent with appropriate surface transduction mechanisms and/or the cytosolic cascades. Such cell lines may be, but are not required to be, prostate derived. Further, such cells or cell lines may be transduced or transfected with an expression vehicle (e.g., a plasmid or viral vector) construct comprising an operable non-translated 5′-promoter containing end of the structural gene encoding the instant gene products fused to one or more antigenic fragments, which are peculiar to the instant gene products, wherein said fragments are under the transcriptional control of said promoter and are expressed as polypeptides whose molecular weight can be distinguished from the naturally occurring polypeptides or may further comprise an immunologically distinct tag or some other detectable marker or tag. Such a process is well known in the art (see Maniatis).
Cells or cell lines transduced or transfected as outlined above are then contacted with agents under appropriate conditions; for example, the agent comprises a pharmaceutically acceptable excipient and is contacted with cells comprised in an aqueous physiological buffer such as phosphate buffered saline (PBS) at physiological pH, Eagles balanced salt solution (BSS) at physiological pH, PBS or BSS comprising serum or conditioned media comprising PBS or BSS and/or serum incubated at 37° C. Said conditions may be modulated as deemed necessary by one of skill in the art. Subsequent to contacting the cells with the agent, said cells are disrupted and the polypeptides of the lysate are fractionated such that a polypeptide fraction is pooled and contacted with an antibody to be further processed by immunological assay (e.g., ELISA, immunoprecipitation or Western blot). The pool of proteins isolated from the “agent-contacted” sample is then compared with a control sample where only the excipient is contacted with the cells and an increase or decrease in the immunologically generated signal from the “agent-contacted” sample compared to the control is used to distinguish the effectiveness of the agent.
Another embodiment of the present invention provides methods for identifying agents that modulate at least one activity of a protein(s) encoded by the genes in Tables 1-6. Such methods or assays may utilize any means of monitoring or detecting the desired activity.
In one format, the relative amounts of a protein of the invention between a cell population that has been exposed to the agent to be tested compared to an un-exposed control cell population may be assayed. In this format, probes such as specific antibodies are used to monitor the differential expression of the protein in the different cell populations. Cell lines or populations are exposed to the agent to be tested under appropriate conditions and time. Cellular lysates may be prepared from the exposed cell line or population and a control, unexposed cell line or population. The cellular lysates are then analyzed with the probe, such as a specific antibody.
Agents that are assayed in the above methods can be randomly selected or rationally selected or designed. As used herein, an agent is said to be randomly selected when the agent is chosen randomly without considering the specific sequences involved in the association of the a protein of the invention alone or with its associated substrates, binding partners, etc. An example of randomly selected agents is the use a chemical library or a peptide combinatorial library, or a growth broth of an organism.
As used herein, an agent is said to be rationally selected or designed when the agent is chosen on a nonrandom basis which takes into account the sequence of the target site and/or its conformation in connection with the agent's action. Agents can be rationally selected or at rationally designed by utilizing the peptide sequences that make up these sites. For example, a rationally selected peptide agent can be a peptide whose amino acid sequence is identical to or a derivative of any functional consensus site.
The agents of the present invention can be, as examples, peptides, small molecules, vitamin derivatives, as well as carbohydrates. Dominant negative proteins, DNAs encoding these proteins, antibodies to these proteins, peptide fragments of these proteins or mimics of these proteins may be introduced into cells to affect function. “Mimic” used herein refers to the modification of a region or several regions of a peptide molecule to provide a structure chemically different from the parent peptide but topographically and functionally similar to the parent peptide (see Grant G A. in: Meyers (ed.) Molecular Biology and Biotechnology (New York, VCH Publishers, 1995), pp. 659-664). A skilled artisan can readily recognize that there is no limit as to the structural nature of the agents of the present invention.
Cells Used for Multi Gene Screening
Many kinds of cells such as primary cells and cell lines can be used for the drug screening methods of the invention. Cells or cell lines derived from prostatic tissues are preferred because the innate gene expression mechanisms of these cells often resemble those of prostatic tissues. Cells used for drug screening can be selected by assaying for the expression of one or more of the marker genes listed in Tables 1-6. The cells which differentially express one or more, or preferably nearly all of the marker genes listed in Tables 1-6 are preferred cells or cell lines for the methods of the invention (see Table 7).
Kits
The invention further includes kits combining, in different combinations, high-density oligonucleotide arrays, reagents for use with the arrays, signal detection and array-processing instruments, gene expression databases and analysis and database management software described above. The kits may be used, for example, to diagnose the disease state of a tissue or cell sample, to monitor the progression of prostate disease states, to identify genes that show promise as new drug targets and to screen known and newly designed drugs as discussed above.
The databases packaged with the kits are a compilation of expression patterns from human and laboratory animal genes and gene fragments (corresponding to the genes of Tables 1-6). In particular, the database software and packaged information include the expression results of Tables 1-6 that can be used in the assays and methods as herein described. In another format, database access is provided to the purchaser or user through an electronic means, e.g., via the Internet or by direct dial-in access.
The kits may used in the pharmaceutical industry, where the need for early drug testing is strong due to the high costs associated with drug development, but where bioinformatics, in particular gene expression informatics, is still lacking. These kits will reduce the costs, time and risks associated with traditional new drug screening using cell cultures and laboratory animals. The results of large-scale drug screening of pre-grouped patient populations, pharmacogenomics testing, can also be applied to select drugs with greater efficacy and fewer side-effects. The kits may also be used by smaller biotechnology companies and research institutes who do not have the facilities for performing such large-scale testing themselves.
Databases and software designed for use with use with microarrays is discussed in Balaban et al., U.S. Pat. No. 6,229,911, a computer-implemented method for managing information, stored as indexed tables, collected from small or large numbers of microarrays, and U.S. Pat. No. 6,185,561, a computer-based method with data mining capability for collecting gene expression level data, adding additional attributes and reformatting the data to produce answers to various queries. Chee et al., U.S. Pat. No. 5,974,164, disclose a software-based method for identifying mutations in a nucleic acid sequence based on differences in probe fluorescence intensities between wild type and mutant sequences that hybridize to reference sequences.
Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the genes, chips, etc. of the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure.
EXAMPLES
Example 1
Gene Chip Expression Analysis
Human tissue was obtained from the transitional zone of the prostate (the junction between the ejaculatory duct and the prostatic urethra) in biopsy samples from normal individuals and from patients with BPH or prostate cancer. BPH was defined histologically in all samples. Normal tissue and asymptomatic BPH samples came from individuals who died of trauma and did not report symptoms. Because BPH is a disease associated with aging, two groups of normal individuals were identified, group 1, ages 20 or under, and group 2, ages 30-50. Patients having BPH with symptoms were defined as those with a need for frequent urination. In these patients, a radical prostatectomy had been performed. Prostate cancer patients provided age-matched tissue samples for symptomatic BPH patients, but were without symptoms and without cancer in the transitional zone under histological examination.
Microarray sample preparation was conducted with minor modifications, following the protocols set forth in the Affymetrix GeneChip Expression Analysis Manual. Frozen tissue was ground to a powder using a Spex Certiprep 6800 Freezer Mill. Total RNA was extracted with Trizol (GibcoBRL) utilizing the manufacturer's protocol. The total RNA yield for each sample was 200-500 μg per 300 mg tissue weight. mRNA was isolated using the Oligotex mRNA Midi kit (Qiagen) followed by ethanol precipitation. Double stranded cDNA was generated from mRNA using the SuperScript Choice system (GibcoBRL). First strand cDNA synthesis was primed with a T7-(dT24) oligonucleotide. The cDNA was phenol-chloroform extracted and ethanol precipitated to a final concentration of 1 μg/ml. From 2 μg of cDNA, cRNA was synthesized using Ambion's T7 MegaScript in vitro Transcription Kit.
To biotin label the cRNA, nucleotides Bio-11-CTP and Bio-16-UTP (Enzo Diagnostics) were added to the reaction. Following a 37° C. incubation for six hours, impurities were removed from the labeled cRNA following the RNeasy Mini kit protocol (Qiagen). cRNA was fragmented (fragmentation buffer consisting of 200 mM Tris-acetate, pH 8.1, 500 mM KOAc, 150 mM MgOAc) for thirty-five minutes at 94° C. Following the Affymetrix protocol, 55 μg of fragmented cRNA was hybridized on the Affymetrix Human 42K array set for twenty-four hours at 60 mpm in a 45° C. hybridization oven. The chips were washed and stained with Streptavidin Phycoerythrin (SAPE) (Molecular Probes) in Affymetrix fluidics stations. To amplify staining, SAPE solution was added twice with an anti-streptavidin biotinylated antibody (Vector Laboratories) staining step in between. Hybridization to the probe arrays was detected by fluorometric scanning (Hewlett Packard Gene Array Scanner). Data was analyzed using Affymetrix GeneChip version 3.0 and Expression Data Mining Tool (EDMT) software (version 1.0).
Differential expression of genes between the BPH and normal prostate samples were determined using the Affymetrix GeneChip human gene chip set by the following criteria: 1) For each gene, Affymetrix GeneChip average difference values were determined by standard Affymetrix EDMT software algorithms, which also made “Absent” (=not specifically detected as gene expression), “Present” (=detected) or “Marginal” (=not clearly Absent or Present) calls for each GeneChip element; 2) all AveDiff values which were less than +20 (positive 20) were raised to a floor of +20 so that fold change calculations could be made where values were not already greater than or equal to +20; 3) median levels of expression were compared between the normal control group and the BPH with symptoms disease group to obtain greater than or equal 2-fold up/down values; 4) The median value for the higher expressing group needed to be greater or equal to 200 average difference units in order to be considered for statistical significance; 5) Genes passing the criteria of #1-4 were analyzed for statistical significance using a two-tailed T test and deemed statistically significant if p<0.05. Tables 1 and 2 list the genes and their levels of differential expression (compared to normal samples) in BPH tissue from patients with symptoms of BPH and in BPH tissue immediately adjacent to malignant prostate tissue isolated from male patients.
Example 2
Expression Profile Analysis
Gene expression profiles between normal sample and BPH patient samples were determined by using the following samples: 10 normal; 7 BPH without symptoms; 8 BPH with cancer; and 8 BPH with symptoms. Gene expression profiles were prepared using the 42K Affymetrix Gene Chip set. The methods used were the same as described in Example 1 with the exception of the criteria to select the marker genes.
The criteria used in this study were as follows; 1) For each gene, Affymetrix GeneChip average difference values were determined by standard Affymetrix EDMT software algorithms, which also made “Absent” (=not specifically detected as gene expression), “Present” (=detected) or “Marginal” (=not clearly Absent or Present) calls for each GeneChip element; 2) all AveDiff values which were less than +20 (positive 20) were raised to a floor of +20 so that fold change calculations could be made where values were not already greater than or equal to +20; 3) mean levels of expression were compared between the normal control group and the BPH with symptoms disease group; 4) genes were arranged by the fold change starting with the largest one (Fold change calculation was determined by using logarithmic values in Example 2); and 5) the top 200 up-regulated genes and bottom 200 down-regulated genes were selected. The genes identified in this study are listed in Tables 3 (normal vs. BPH with symptoms, up regulated) and 4 (normal vs. BPH with symptoms, down regulated, values are negative fold-change from normal).
Example 3
Selection of Cell Lines Used for Multi Gene Screening
A number of cultured cell lines were tested to determine the similarity in gene expression profiles to BPH tissue. Cells were cultured in 6-well plates using the appropriate medium for each cell line. After reaching 90% confluency, cells were lysed with Trizol (GiboBRL) and total RNA was extracted. mRNA was then isolated, cDNA and cRNA was synthesized, and gene expression levels were determined by the Affymetrix Human 42K Gene Chip set as described in more detail above.
The gene expression profiles were compared with those of prostatic tissue samples. A panel of 61 genes whose expression levels were up-regulated in BPH with symptoms compared with normal samples and with small variation among samples (within BPH samples and within normal samples) were assayed. The group of genes whose signal intensity was more than 100 in each cell line is summarized in Table 1. A panel of 43 genes whose expression levels were down-regulated in BPH patient with small variation among samples was also assayed. The group of genes whose signal intensity in Affymetrix Gene Chip was “Present call” is also included in Table 1. Similarly, genes whose expression level is up- or down-regulated in patients with BPH and cancer, compared to normal controls, are listed in Table 2.
Forty-eight to 58% of genes applied for this analysis were expressed in the cell lines of Table 7. These results indicate that cell lines, BRF-55T (Biological Research Faculty & Facility Inc.), PZ-HPV7 (ATCC; CRL-2221), BPH-1 (S. W. Hayward et al., In Vitro Cell Dev. Biol. 31A, 14-24, 1995) and LNCaP (ATCC; CRL-1740) can be used as a BPH—like cell population to screen for compounds which are capable of modulating gene expression profiles from the disease state to a normal state using the genes of Tables 1-6. In particular, BRF-55T is a useful cell line for screening in the assays of the invention, because 58% genes of the assayed genes were differentially expressed in BRF-55T as compared to BPH with symptoms tissue.
Example 4
Cluster Analysis of Up- or Down-regulated Genes in BPH
Cluster analysis of the expression results from a large number of genes is often problematic due to variations in the standardization of the gene expression data. To compensate for these variations, a subset of differentially expressed genes was selected by a modified analysis procedure.
In a first step, a gene list comparing normal vs. disease samples was generated by two kinds of comparisons. First, genes were selected that displayed a greater than or equal to mean 2-fold up or down regulation using average difference expression values and with p<0.05. Second, genes were selected by ANOVA comparing the normal group of samples with the disease group and with a t value of >3 in the up or down direction. These lists were then combined to create an expression profile characteristic of normal controls and one characteristic of disease in which specific genes are found to be up or down regulated in disease when compared with normal controls.
In preparation for clustering analysis to identify subgroups of genes that show statistically similar expression patterns, average difference values for the selected genes were normalized across all samples (normal and disease combined) using the following formula:

Normalization data=(X−Xmean)/Sx 

Where Sx is variance (:STD)
This converts the mean expression value for each gene to 0 and the high and low values to 1 and −1, respectively. Thus, genes with high absolute expression values when compared with genes with low absolute expression values would not skew the comparisons when clustering algorithms are applied.
The measurement of the cluster space distance was determined by using the correlation coefficient (1-r) method and clustering was performed using Ward's method (Ward, J. H. (1963) Journal of American Statistical Association, 58. 236.)
The clustering was validated by observing whether multiple elements representing the same genes showing the same direction of expression change (i.e., either up or down) tend to cluster together. To test this standardization and clustering protocol, the expression levels for genes that are represented by more than one element on the 42K gene chip set were analyzed to determine whether the multiple elements for a single gene could be clustered together. For example, tryptase, also known as alpha tryptase or beta (tryptase II) is represented by two separate elements on the 42K human gene chip. This gene is registered with 2 different element names 41268 (5), M33493_s_at (code name, Up-170) and 26389 (3), rc_AA131322—s_at (code name, Up-010).
It was found that the best analysis means for decreasing measurement errors between these two elements is by the Ward method as it gave the most consistent results when compared to other clustering methods. These analysis methods may be incorporated into software or computer readable storage media for storing a computer programmer software.
Example 5
Selection of 60 Marker Genes
A panel of 60 representative marker genes (listed in Table 5) out of 400 marker genes listed in Tables 3 and 4 can be used in the assays and methods of the invention. The 60 marker genes were selected based on following criteria: (1) expression level is changed greatly in BPH patient samples compared with normal samples; (2) variation of expression levels within BPH samples and within normal samples is small; and (3) expression levels resembling BPH with symptoms are detected in cell line BRF-55T.
Example 6
Gene Expression Analysis of Select Genes
The expression levels of three genes from Tables 1-5 (the genes encoding cellular retinol binding protein, S100 calcium binding protein and PSMA) were assayed in various tissues and prostate samples by PCR as described in Example 7 (see FIGS. 1-6). Each sample was assayed for the level of GAPDH and mRNA corresponding to cellular retinol binding protein, S100 calcium binding protein or PSMA. As seen in FIGS. 1-6, these three genes are differentially regulated or expressed in BPH tissue from patients with or without symptoms and from BPH tissue from patients with prostate cancer (compared to normal prostate tissue). All three genes are therefore useful markers in the assays of the invention, such as the assays to measure the effect of an agent on BPH or the assays to detect or diagnose the occurrence or progression of BPH.
Example 7
Drug Screening Assays
The expression profiles for normal controls and disease samples described above can be used to identify compound hits from a compound library. A hit may be, but is not necessarily, defined as one of three kinds of results:
1) The expression of an individual gene is changed in the direction of normal (i.e., if UP in disease, then down-hit, if down in disease, then up=hit). The stronger the modulation of an individual gene to a normnal phenotype, the stronger the hit status for the compound against that gene.
2) The expression of genes that sub cluster together is evaluated for an overall pattern of modulation to a normal expression profile. The more genes in a subcluster that are modulated to a normal phenotype, the stronger the hit status for the compound against that subcluster. A subcluster may represent common or interacting cellular pathways.
3) The overall expression profile of all of the genes being screened is evaluated for modulation to normal. The more genes that are modulated to a normal phenotype, the stronger the hit status for the compound against the entire gene set.
As described above, if a compound modulates the gene expression pattern of the screening system cells more towards any disease phenotype, then it can be used as a molecular probe to find binding proteins and/or define disease-associated cellular pathways.
As an example, candidate agents and compounds are screened for their ability to modulate the expression levels of cellular retinol binding protein, S100 calcium binding protein and PSMA by exposing a prostate cell line or cell line from BPH tissue to the agent and assaying the expression levels of these genes by real time PCR. Real time PCR detection is accomplished by the use of the ABI PRISM 7700 Sequence Detection System. The 7700 measures the fluorescence intensity of the sample each cycle and is able to detect the presence of specific amplicons within the PCR reaction. Each sample is assayed for the level of GAPDH and mRNA corresponding to cellular retinol binding protein, S100 calcium binding protein and PSMA. GAPDH detection is performed using Perkin Elmer part#402869 according to the manufacturer's directions. Primers were designed for the three genes by using Primer Express, a program developed by PE to efficiently find primers and probes for specific sequences ((1) N91971-FAM PROBE Forward: 5′-CAT ggC TTT gTT TTA AgA AAA ggA A-3′; Reverse: 5′-AgC CAC CCC CAg gCA T-3′; Probe: 5′-FAM-AgT gAC AAA gCC AAg AgA CAg ACT CTg CTA ACA-TAMRA-3′; (2) X65614-SYBR; Forward: 5′-AAA gAC AAg gAT gCC gTg gAT-3′; Reverse 5′-AgC CAC gAA CAC gAT gAA CTC-3′; (3) M99487-SYB; Forward 5′-Tgg CTC AgC ACC ACC Aga T-3′; Reverse: 5′-TTC Cag TAA AgC Cag gTC CAA-3′)
These primers are used in conjunction with SYBR green (Molecular Probes), a nonspecific double stranded DNA dye, to measure the expression level mRNA corresponding to the genes, which is normalized to the GAPDH level in each sample.
Normalized expression levels from cells exposed to the agent are then compared to the normalized expression levels in control cells. Agents that modulate the expression of one or more the genes may be further tested as drug candidates in appropriate BPH in vitro or in vivo models.
Example 8
Comparative Assays
The expression of a panel of marker genes was compared, in the same subjects as disclosed in Example 2, in a pairwise fashion between the BPH patients with (BPHWS) or without (BPHNoS) symptoms versus normal (Normal) controls and asymptomatic BPH patients with cancer (Cancer). In every case, the tissue was excised from the junction between the ejaculatory duct and the prostatic urethra in the transition zone of the prostate. In particular, BPH tissue from patients with early stage prostate cancer was carefully excised away from the cancer lesion macroscopically, and their histological diagnosis was confirmed microscopically.
Pairwise comparisons between the subject groups were subjected to an Analysis of Variance (ANOVA) model. P-values corresponding to each of six possible pairwise comparisons among the four sample groups were then determined for each gene. Table 6 depicts Affymetrix fragments, along with their GenBank accession number, which have p<0.001 for two or more of the pairwise comparisons.
A Principal Component Analysis (PCA) was performed to show that this gene set serves as a basis to discriminate among the various groups of samples. The samples are plotted using the scores for the first three principal components. Each of the four sample groups can be clearly distinguished from one another in this analysis (FIG. 7A). Component 1 (36% of the variability) discriminates between Normal and asymptomatic BPH versus BPH cancer and symptomatic BPH. Component 2 (10% of the variability) distinguishes Normal from asymptomatic BPH, and Component 3 (8% of the variability) distinguishes BPH cancer from symptomatic BPH.
FIG. 7B shows a two-dimensional representation of the PCA, with Component 1 plotted against Components 2+3. Each of the four sample groups is clustered in a different quadrant of this figure. Within each sample group, there does not appear to be any age-related clustering of samples. Further, since there is an overlap of ages between the samples groups, it does not appear that age was a confounding factor for the analysis based on this gene set. Because BPH is perceived as a natural consequence of aging, two subgroups of normal individuals were initially identified. A ‘younger’ set included individuals ranging in age from 13-20 years while the ‘older’ set ranged from 31-51 years. However, because the two subsets appeared to be indistinguishable at the molecular level, they were grouped together and in all subsequent analysis referred to as ‘Normal’ group.
Another finding was that the intra-group variability (i.e., the tightness of clustering) differed between the four groups (FIG. 7A). Normal patients exhibited the least intra-group variability, followed by asymptomatic BPH and symptomatic BPH with BPH cancer patients exhibiting the most patient-to-patient variability. On the other hand, with regard to the inter-group variation, the asymptomatic BPH group appeared to be more similar to the normal group than to symptomatic BPH (FIG. 7B).
Asymptomatic BPH samples were obtained from individuals that died from other causes and had no records of being treated for BPH but had histological evidence for BPH when examined retrospectively. Since asymptomatic samples clearly exhibit the BPH phenotype at the microscopic level, one would expect the two BPH groups to exhibit more similarity than disparity. Similarly, that the BPH cancer group is distinct from asymptomatic BPH but is more similar to the symptomatic BPH group (FIG. 7B). Since transition zone tissue from patients with prostate cancer with no clinical symptoms of BPH was analyzed from these patients, this group of patients would be expected to appear similar to normal or asymptomatic BPH. The fact that the BPH cancer group can be distinguished from every other group is also an unexpected finding. Subsequent to this PCA, additional samples were studied to extend these findings. These included two normals and three symptomatic BPH patients. Using the same set of genes, a PCA was performed with these additional samples. In FIG. 7C, the two new normal (Norm) samples group with the previous normal samples and the three new symptomatic BPH (BPH) samples group with the other symptomatic BPH samples.
Example 9
Diagnostic Assays
The expression profiles of one or more of the individual genes of Tables 1-6 are used as molecular or diagnostic markers to evaluate the disease status of a patient sample. In one embodiment, a patient prostate tissue sample is processed as described herein to produce total cellular or mRNA. The RNA is hybridized to a chip comprising probes that specifically hybridize to one or more, or two or more of the genes in Tables 1-6. The overall expression profile generated, or the expression levels of individual genes are then compared to the profiles as described in Tables 1-6 to determine the disease or hyperplastic state of the patient sample.
Although the present invention has been described in detail with reference to examples above, it is understood that various modifications can be made without departing from the spirit of the invention. Accordingly, the invention is limited only by the following claims. All cited patents, applications, GenBank Accession numbers and publications referred to in this application are herein incorporated by reference in their entirety.







TABLE 1







Normal1-Normal2 vs BPH-With Symptoms


















Fold-








change




SEQ ID


N1-N2 vs
p-value



Affymetrix element
NO:
Genbank ID
Genbank Name
With
N1-N2 vs With

















Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



RC_AA463726_s_at
386
AA463726
JM27 proteinXp11.23
14.9
0.018598344



RC_AA057195_at
47
AA057195
Homo sapiens mRNA; cDNA
14.0
0.029325045






DKFZp586M121 (from clone






DKFZp586M121)



V01512_rna1_at
993
V01512
v-fos FBJ murine osteosarcoma viral
13.1
0.001027561






oncogene homolog14q24.3



RC_AA427622_s_at
311
AA427622
collagen, type XIII, alpha 110q22
11.6
0.00074954



RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral
11.4
0.000631487






oncogene homolog14q24.3



RC_AA465491_at
391
AA465491
Mad4 homolog4p16.3
11.4
0.031024189



RC_AA620825_at
454
AA620825
ESTs
11.3
0.010915901



RC_R93908_at
865
R93908
ESTs
11.3
0.019994337



RC_AA461300_at
381
AA461300
ESTs
11.0
0.007061759



N40141_at
743
N40141
JM27 proteinXp11.23
10.9
0.013756347



RC_R25410_at
814
R25410
ESTs
7.7
0.01851753



L49169_at
649
L49169
FBJ murine osteosarcoma viral
7.4
0.041523744






oncogene homolog B19q13.3



RC_AA279760_at
193
AA279760
ESTs
7.0
0.024411468



RC_T90889_at
927
T90889
ESTs
6.5
0.015666863



U62015_at
978
U62015
insulin-like growth factor binding
6.0
0.002843661






protein 101p22-p31



RC_AA188981_at
112
AA188981
highly expressed in cancer, rich in
5.9
0.002280479






leucine heptad repeats



D83018_at
513
D83018
nel (chicken)-like212q13.11-q13.12
5.6
0.000570952



RC_H64493_f_at
590
H64493
immunoglobulin gamma 3 (Gm
5.6
0.01109802






marker)14q32.33



X52541_at
1064
X52541
early growth response 15q31.1
5.2
0.002428259



M57466_s_at
690
M57466
major histocompatibility complex,
5.1
0.002137399






class II, DP beta 16p21.3



J03507_at
621
J03507
complement component 75p13
4.9
1.36616E−05



RC_N30198_at
733
N30198
ESTs
4.8
0.003366461



RC_T78398_at
913
T78398
EST
4.8
0.033293747



RC_H17550_at
559
H17550
ESTs
4.7
0.047828622



RC_T67053_f_at
909
T67053
immumoglobulin lambda gene
4.5
0.045107075






cluster22q11.1-q11.2



RC_AA598982_s_at
429
AA598982
trophininXp11.22-p11.21
4.3
0.000902336



RC_AA256268_at
175
AA256268
ESTs
4.2
0.001506239



HG3543-HT3739_at
675
M29645
insulin-like growth factor 2
4.1
0.017253126






(somatomedin A)11p15.5



RC_N91971_f_at
791
N91971
retinol-binding protein 1, cellular3q23
4.1
0.02528773



RC_AA479286_at
403
AA479286
ESTs
4.0
0.028009544



M62831_at
695
M62831
immediate early protein19
4.0
0.000484086



RC_F02992_at
526
F02992
ESTs, Weakly similar to unknown
3.9
0.031845412





[M. musculus]



RC_H86112_f_at
600
H86112
KIAA0471 geneproduct1q24-q25
3.8
0.004155259



RC_AA436616_at
335
AA436616
ESTs
3.8
0.017156387



RC_T62857_at
903
T62857
ESTs
3.7
0.000301735



RC_AA281345_f_at
201
AA281345
immediate early protein19
3.6
0.001679723



U21128_at
953
U21128
lumican12q21.3-q22
3.6
2.19529E−05



U30521_at
960
U30521
P311 protein
3.6
0.001150397



RC_N58172_at
757
N58172
ESTs
3.5
0.043092144



RC_T03229_f_at
874
T03229
EST
3.5
0.031101935


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



X06700_s_at
1049
X06700
collagen, type III, alpha 1 (Ehlers-
3.5
0.008472599






Danlos syndrome type IV, autosomal






dominant)2q31



RC_Z39904_at
1111
Z39904
Homo sapiens clone 23555 mRNA
3.4
0.002949046






sequence



RC_T23622_at
886
T23622
ESTs
3.4
0.002174281



J00231_f_at
617
J00231
immunoglobulin gamma 3 (Gm
3.4
0.009322568






marker)14q32.33



RC_AA028092_s_at
17
AA028092
transcription factor 216pter-qter
3.4
3.13963E−06



RC_AA252528_at
170
AA252528
ESTs
3.4
0.000225707



L33799_at
645
L33799
procollagen C-endopeptidase
3.3
0.018469201






enhancer7q22



RC_F09748_s_at
537
F09748
Homo sapiens mRNA; cDNA
3.2
0.02728166






DKFZp586K1220 (from clone






DKFZp586K1220)



RC_T64223_s_at
907
T64223
carboxypeptidase A3 (mast cell)3q21
3.2
0.027915742






q25



RC_AA402903_f_at
263
AA402903
immunoglobulin gamma 3 (Gm
3.2
0.044721116






marker)14q32.33



RC_F13763_at
542
F13763
ESTs
3.1
0.000503701



RC_AA488432_at
412
AA488432
phosphoserine phosphatase7p21-
3.1
0.020997503






p15



RC_AA486072_i_at
410
AA486072
small inducible cytokine A5
3.1
0.025877597






(RANTES)17q11.2-q12



RC_N22006_s_at
719
N22006
EST
3.1
0.00148561



RC_AA257093_r_at
178
AA257093
T-cell receptor, beta cluster7q35
3.1
1.71945E−07



RC_AA609943_at
449
AA609943
ESTs
3.0
0.029360518



RC_T23490_s_at
885
T23490
ESTs
3.0
0.008741411



D13628_at
476
D13628
angiopoietin 18q22.3-q23
2.9
0.006228419



M73720_at
702
M73720
carboxypeptidase A3 (mast ceLl)3q21
2.9
0.006585391






q25



Z74616_s_at
1123
Z74616
collagen, type I, alpha 27q22.1
2.8
0.008750622



AA082546_at
54
AA082546
ESTs
2.8
0.019771126



RC_AA284920_at
213
AA284920
ESTs
2.7
0.019738239



RC_AA599365_at
434
AA599365
decorin12q23
2.7
0.001295936



X57025_at
1066
X57025
insulin-like growth factor 1
2.7
0.022341194






(somatomedin C)12q22-q23



X51345_at
1062
X51345
jun B proto-oncogene19p13.2
2.7
0.036487159



RC_N67876_s_at
773
N67876
insulin-like growth factor 1
2.7
0.035216134






(somatomedin C)12q22-q23



RC_AA609504_at
444
AA609504
KIAA0405 gene product
2.7
0.020881055



RC_N69207_at
776
N69207
ESTs, Moderately similar to !!!! ALU
2.6
0.041315387






SUBFAMILY SB2 WARNING ENTRY






!!!! [H. sapiens ]



M87789_s_at
704
M87789
immunoglobulin gamma 3 (Gm
2.6
0.038916248






marker)14q32.33



HG3510-HT3704_at
1055
X12795
nuclear receptor subfamily 2, group
2.6
0.016151338






F, member 15q14



RC_T64211_at
906
T64211
ESTs, Weakly similar to pancortin-1
2.6
0.006233291






8 M. musculus]



U90552_s_at
988
U90552
butyrophilin, subfamily 3, member
2.6
0.004564282






A16p23



M34516_r_at
684
M34516
immunoglobulin lambda-like
2.6
0.049767038






polypeptide 322q11.2


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



RC_T23468_at
884
T23468
ESTs
2.5
0.00250737



RC_AA173223_at
108
AA173223
ESTs, Weakly similar to !!!! ALU
2.5
0.007080285






SUBFAMILY SQ WARNING ENTRY






!!!! [H. sapiens ]



RC_T49061_at
894
T49061
ESTs
2.5
0.039642391



RC_AA234095_at
144
AA234095
ESTs
2.5
0.003152859



RC_F01920_s_at
520
F01920
pre-B-cell leukemia transcription
2.5
0.002088945






factor 39q33-q34



RC_N91461_at
789
N91461
ESTs
2.4
0.01015467



RC_N67575_s_at
771
N67575
osteoglycin (osteoinductive factor)
2.4
0.004044061



RC_AA151210_at
89
AA151210
ESTs
2.4
0.011476541



AA156897_s_at
97
AA156897
Homo sapiens mRNA; cDNA
2.4
0.033974981






DKFZp564I1922 (from clone






DKFZp564I1922)



W73859_at
1028
W73859
transcription factor 216pter-qter
2.4
0.024640626



RC_H68097_at
592
H68097
EST
2.4
0.04870874



RC_AA436618_at
336
AA436618
ESTs
2.4
0.02483165



M33493_s_at
680
M33493
tryptase, beta (tryptase II)16p13.3
2.4
0.02689938



AB002340_at
461
AB002340
KIAA0342 gene product
2.3
0.000748796



RC_AA446661_at
347
AA446661
ESTs
2.3
0.011980248



RC_AA084138_at
55
AA084138
ESTs
2.3
1.16025E−05



RC_N59866_at
761
N59866
ESTs, Weakly similar to putative
2.3
0.002042263






p150 [H. sapiens ]



RC_R42424_at
832
R42424
ESTs
2.3
0.003173074



RC_N39415_at
742
N39415
osteoglycin (osteoinductive factor)
2.3
0.001310764



J03464_s_at
620
J03464
collagen, type I, alpha 27q22.1
2.3
0.006791534



RC_AA205376_at
121
AA205376
KIAA0471 gene product1q24-q25
2.3
0.023123837



RC_H95960_at
606
H95960
secreted protein, acidic, cysteine-rich
2.3
0.008509182






(osteonectin)5q31.3-q32



D28137_at
484
D28137
bone marrow stromal cell antigen
2.3
0.031127266






219p13.2



RC_N79778_at
784
N79778
extracellular matrix protein 2, female
2.3
0.045073744






organ and adipocyte specific9q22.3



RC_N98485_s_at
800
N98485
forkhead (Drosophila)-like 66p25.3
2.3
0.033372862



M98539_at
715
M98539
prostaglandin D2 synthase (21 kD,
2.2
0.005442674






brain)9q34.2-q34.3



RC_AA205724_at
123
AA205724
ESTs
2.2
0.006183612



U85625_at
986
U85625
Homo sapiens ribonuclease 6
2.2
0.001245066






precursor, mRNA, complete cds.



RC_R37588_s_at
821
R37588
RAB2, member RAS oncogene
2.2
0.00219386






family-like6p21.3



RC_AA046426_at
35
AA046426
Cdc42 effector protein 3
2.2
0.005788723



RC_AA256294_at
176
AA256294
ESTs
2.2
0.002425605



RC_AA599120_at
431
AA599120
SWI/SNF related, matrix associated,
2.2
0.04


2979241






actin dependent regulator of






chromatin, subfamily e, member 1



RC_W60186_at
1018
W60186
ESTs
2.2
0.028494835



RC_AA599216_at
432
AA599216
collapsin response mediator protein
2.2
0.040523744






14p16.1-p15



RC_AA450324_at
360
AA450324
ESTs
2.1
0.009094567



M31994_at
678
M31994
Homo sapiens aldehyde
2.1
0.001561218






dehydrogenase (ALDH1) gene


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



RC_AA402930_at
264
AA402930
ESTs
2.1
0.000114627



M91029_cds2_at
706
M91029
Human AMP deaminase isoform L
2.1
0.02494373






(AMPD2) mRNA, exons 6–18, partial






cds



RC_AA450114_at
358
AA450114
ESTs, Weakly similar to 17beta-
2.1
4.87556E−06






hydroxysteroid dehydrogenase






[H. sapiens ]



D62584_at
501
D62584
osteoglycin (osteoinductive factor)
2.1
0.000157116



RC_AA621634_at
457
AA621634
ESTs
2.1
0.02297009



RC_AA312946_s_at
228
AA312946
ESTs
2.1
3.51075E−05



X07438_s_at
1054
X07438
Human DNA for cellular retinol
2.1
0.039015947






binding protein (CRBP)



RC_N53447_at
751
N53447
integral membrane protein 2CXq21.1-
2.1
0.009032297






21.2



RC_AA281591_at
202
AA281591
Homo sapiens mRNA; cDNA
2.0
0.016660714






DKFZp586B211 (from clone






DKFZp586B211)



RC_R71395_at
854
R71395
ESTs, Moderately similar to
2.0
0.046231847






alternatively spliced product using






exon 13A [H. sapiens ]



RC_T53590_s_at
899
T53590
cytochrome P450, subfamily XIA
2.0
0.00282074






(cholesterol side chain






cleavage)15q23-q24



RC_AA293489_at
224
AA293489
KIAA0638 protein
2.0
0.006966532



RC_AA447707_s_at
351
AA447707
KIAA1055 protein
2.0
0.001248537



RC_AA235618_f_at
149
AA235618
ESTs
2.0
0.012481746



RC_N68350_at
775
N68350
ESTs
2.0
0.035156598



RC_H81379_s_at
596
H81379
ESTs, Moderately similar to
2.0
0.01148429






KIAA0438 [H. sapiens ]



RC_D51060_s_at
495
D51060
Jun activation domain binding
2.0
0.016668951






protein1p32-p31



U72649_at
983
U72649
B-cell translocation gene 2
2.0
0.020660388






(pheochromacytoma cell-3)1q32



RC_AA287389_at
216
AA287389
ESTs
2.0
0.002741873



RC_AA621367_at
456
AA621367
ESTs
2.0
0.004871903



J03040_at
619
J03040
secreted protein, acidic, cysteine-rich
2.0
0.006303994






(osteonectin)5q31.3-q32



RC_AA291676_s_at
219
AA291676
non-metastatic cells 5, protein
2.0
0.027480479






expressed in (nucleoside-






diphosphate kinase)5q23-q31



RC_N63536_at
763
N63536
ESTs
2.0
0.000634305



RC_AA411952_at
282
AA411952
UDP-Gal:betaGlcNAc beta 1,3-
2.0
0.011858934






galactosyltransferase, polypeptide






33q25



RC_AA252802_s_at
171
AA252802
Human mRNA for TI-227H
2.0
0.041027635



RC_AA382275_at
244
AA382275
ESTs
2.0
0.00087437



AA093923_at
63
AA093923
tissue inhibitor of metalloproteinase
2.0
0.046200886






217q25



M11313_s_at
654
M11313
alpha-2-macroglobulin12p13.3-p12.3
2.0
0.013660595



RC_AA398280_at
248
AA398280
ESTs
2.0
0.044320644



RC_N51529_at
747
N51529
ESTs
2.0
0.006276979



H49440_at
578
H49440
nudix (nucleoside diphosphate linked
2.0
0.013879331






moiety X)-type motif 36p21.2


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



RC_T33263_s_at
890
T33263
KIAA0320 protein
2.0
0.009994615



RC_T89160_r_at
921
T89160
ESTs
2.0
0.005289266



RC_W56792_at
1016
W56792
ESTs, Weakly similar to
2.0
0.026130523






serine/threonine protein kinase TAO1






8 R. norvegicus]



RC_R60056_at
849
R60056
ESTs, Moderately similar to
2.0
0.001585076






alternatively spliced product using






exon 13A [H. sapiens ]


Down-
RC_AA398908_at
251
AA398908
Human Chromosome 16 BAC clone
−21.7
0.007918174


regulated



CIT987SK-A-61E3



RC_AA460914_at
380
AA460914
ESTs
−15.8
0.013659536



RC_T40895_at
892
T40895
ESTs
−12.6
0.002430219



RC_R71792_s_at
855
R71792
ESTs, Moderately similar to FAT-
−9.8
0.01438632






SPECIFIC PROTEIN FSP27






8 M. musculus]



RC_N80129_i_at
785
N80129
metallothionein 1L16q13
−8.7
0.002816872



X66141_at
1078
X66141
myosin, light polypeptide 2,
−8.0
0.03928942






regulatory, cardiac, slow12q23-q24.3



AA234634_f_at
145
AA234634
CCAAT/enhancer binding protein
−7.4
0.000589696






(C/EBP), delta8p11.2-p11.1



U78294_at
985
U78294
arachidonate 15-lipoxygenase,
−6.8
0.017271608






second type



RC_AA457566_at
375
AA457566
ESTs
−6.6
0.029644622



X93036_at
1093
X93036
phospholemman-like, expressed in
−6.2
0.011323909






breast tumors, 8kD



X57129_at
1067
X57129
H1 histone family, member 26p21.3
−6.1
0.004161922



HG1067-HT1067_r_at
671
M22406
Human intestinal mucin mRNA,
−5.8
0.007202185






partial cds, clone SMUC 42



X65614_at
1076
X65614
S100 calcium-binding protein P4p16
−5.8
0.006892572



RC_AA609006_at
440
AA609006
ESTs
−5.7
0.015701354



J03910_rna1_at
622
J03910
metallothionein 1G16q13
−5.7
0.003506953



RC_H94471_at
604
H94471
occludin5q13.1
−5.6
0.025014274



AB000584_at
459
AB000584
prostate differentiation factor
−5.4
0.003235425



RC_W88568_at
1035
W88568
glycogenin 2Xp22.3
−5.1
0.048573115



V00594_at
992
V00594
metallothionein 2A16q13
−5.0
0.000721258



RC_T73433_s_at
912
T73433
angiotensinogen1q41-qter
−4.9
0.012700144



RC_N94303_at
797
N94303
ESTs
−4.5
4.88059E−05



RC_AA419011_at
296
AA419011
Homo sapiens mRNA; cDNA
−4.1
0.013801595






DKFZp586D0823 (from clone






DKFZp586D0823)



RC_N32748_at
736
N32748
ESTs
−4.1
0.018749207



RC_AA053424_at
40
AA053424
ESTs, Weakly similar to mucin Muc3
−4.0
0.001235197






[R. norvegicus]



RC_AA599331_at
433
AA599331
ESTs
−4.0
0.005480655



M99487_at
716
M99487
folate hydrolase (prostate-specific
−3.9
0.013268152






membrane antigen) 111p11.2



RC_F02245_at
522
F02245
monoamine oxidase AXp11.4-p11.3
−3.8
0.002950391



X76717_at
1087
X76717
metallothionein 1L16q13
−3.7
0.000868707


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



X64177_f_at
1075
X64177
metallothionein 1H16q13
−3.7
0.002089771



RC_AA599522_r_at
437
AA599522
squamous cell carcinoma antigen
−3.6
0.012643918






recognised by T cells



L77701_at
651
L77701
human homolog of yeast
−3.6
0.003341007






mitochondrial copper recruitment






gene



RC_D11824_at
474
D11824
ESTs, Moderately similar to weak
−3.6
0.000803294






similarity to Arabidopsis thaliana






ubiquitin-like protein 8 [C. elegans]



RC_AA410311_at
275
AA410311
ESTs
−3.5
0.001234064



RC_AA457235_at
373
AA457235
ESTs
−3.5
0.012177965



RC_N93798_at
796
N93798
protein tyrosine phosphatase type
−3.5
0.007340453






IVA, member 3



RC_AA416762_s_at
291
AA416762
nuclear receptor subfamily 1, group
−3.5
0.010404304






H, member 219q13.3-19q13.3



RC_F03969_at
528
F03969
ESTs, Weakly similar to tumorous
−3.5
0.011826812






imaginal discs protein Tid56 homolog






[H. sapiens ]



RC_AA045487_at
31
AA045487
ESTs
−3.4
0.025187615



RC_Z38744_at
1108
Z38744
putative gene product13
−3.4
2.30674E−05



RC_N92502_s_at
794
N92502
ESTs, Moderately similar to HERV-E
−3.4
0.02301359






integrase [H. sapiens ]



RC_R91484_at
863
R91484
ESTs
−3.4
8.2306E−05



RC_AA165313_at
104
AA165313
ESTs
−3.3
0.028364404



RC_AA182030_at
110
AA182030
ESTs
−3.3
0.019770486



RC_T94447_s_at
928
T94447
ESTs, Moderately similar to (defline
−3.3
0.001427294






not available 4335935) [M. musculus]



RC_W20486_f_at
995
W20486
ESTs
−3.3
0.002892697



RC_R16983_at
811
R16983
ESTs
−3.2
0.000912559



RC_AA504805_s_at
424
AA504805
interferon stimulated gene
−3.2
0.003905701






(20kD)15q26



RC_T90190_s_at
925
T90190
H1 histone family, member 26p21.3
−3.2
0.020618793



RC_AA135870_at
79
AA135870
ESTs
−3.1
0.04609197



RC_H99035_at
612
H99035
ESTs
−3.1
0.000191451



RC_R28370_at
815
R28370
ESTs
−3.1
0.024606319



RC_T40995_f_at
893
T40995
alcohol dehydrogenase 3 (class I),
−3.1
0.024064044






gamma polypeptide4q21-q23



MIP1-B_at
1124
M35590
karyopherin (importin) beta 2
−3.1
0.005882353



RC_AA447522_at
349
AA447522
ESTs, Highly similar to differentially
−3.1
0.003518059






expressed in Fanconi anemia






[H. sapiens ]



RC_AA461453_at
382
AA461453
ESTs, Moderately similar to Cab45a
−3.0
0.021949087






[M. musculus]



AA429539_f_at
318
AA429539
ESTs
−3.0
0.017623102



RC_AA476944_at
394
AA476944
ESTs
−3.0
0.019974254



RC_N80129_f_at
785
N80129
metallothionein 1L16q13
−3.0
0.000219038



RC_N26904_at
731
N26904
ESTs, Weakly similar to
−2.9
0.006305062






FK506/rapamycin-binding protein






FKBP13 precursor [H. sapiens ]



RC_AA505136_at
426
AA505136
ESTs
−2.9
0.005400284



AA455001_s_at
368
AA455001
ESTs
−2.9
2.1534E−05



RC_W70131_at
1024
W70131
ESTs
−2.9
0.005764635


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



RC_AA043349_at
27
AA043349
ESTs
−2.9
0.016983419



U02020_at
936
U02020
pre-B-cell colony-enhancing factor
−2.9
0.003324497



U52969_at
970
U52969
Purkinje cell protein 421q22.2-q22.3
−2.8
0.00078638



RC_H22453_at
564
H22453
ESTs
−2.8
0.000410695



RC_N22620_at
722
N22620
ESTs
−2.8
0.005507089



RC_N64683_at
764
N64683
ESTs
−2.8
0.00378977



RC_N24761_at
725
N24761
ESTs
−2.8
0.004837185



RC_AA464728_s_at
388
AA464728
ESTs
−2.8
0.004669897



RC_H83380_at
598
H83380
ESTs
−2.7
0.016543793



M30894_at
676
M30894
T-cell receptor, gamma cluster7p15-
−2.7
0.034153167






p14



RC_H81070_f_at
595
H81070
Human metallothionein (MT)I-F gene
−2.7
0.022654931



J00073_at
615
J00073
actin, alpha, cardiac muscle15q11-
−2.7
0.029724167






qter



RC_H05084_at
547
H05084
ESTs, Weakly similar to ORF
−2.7
0.016965435






YDL055c [S. cerevisiae]



AA045870_at
34
AA045870
Homo sapiens mRNA; cDNA
−2.7
0.005480167






DKFZp564A072 (from clone






DKFZp564A072)



RC_T68873_f_at
911
T68873
metallothionein 1L16q13
—2.7
0.001140431



RC_N72253_at
778
N72253
ESTs
−2.7
0.001832591



RC_AA447977_s_at
352
AA447977
Homo sapiens mRNA; cDNA
−2.7
0.001255304






DKFZp564A072 (from clone






DKFZp564A072)



RC_H18947_at
561
H18947
ESTs
−2.7
0.00193501



RC_H77597_f_at
594
H77597
metallothionein 1H16q13
−2.7
0.001560766



RC_H94475_s_at
605
H94475
alpha-2-plasmin inhibitor17pter-p12
−2.6
0.01435663



RC_AA025370_at
15
AA025370
KIAA0872 protein
−2.6
0.013924142



RC_AA443114_at
343
AA443114
ESTs, Moderately similar to PIM-1
−2.6
0.000703574






PROTO-ONCOGENE






SERINE/THREONINE-PROTEIN






KINASE [M. musculus]



RC_F09684_at
535
F09684
ESTs
−2.6
0.000107291



RC_AA031360_s_at
20
AA031360
ESTs
−2.6
0.047293081



RC_AA416685_at
290
AA416685
UNC13 (C. elegans)-like9p11-p12
−2.6
0.023296279



D29805_at
487
D9805
UDP-Gal:betaGlcNAc beta 1,4-
−2.6
2.3562E−05






galactosyltransferase, polypeptide






19p13



RC_H58873_s_at
583
H58873
solute carrier family 2 (facilitated
−2.5
0.000710917






glucose transporter), member 11p35-






p31.3



M10942_at
652
M10942
metallothionein 1E (functional)16q13
−2.5
0.017370635



RC_T03593_at
875
T03593
ESTs
−2.5
0.006239127



RC_N95495_at
799
N95495
small inducible cytokine A5
−2.5
0.002392984






(RANTES)17q11.2-q12



RC_AA017063_r_at
8
AA017063
ESTs, Highly similar to Miz-1 protein
−2.5
0.048093776






[H. sapiens ]



RC_R00144_at
801
R00144
ESTs
−2.5
0.018222161



RC_AA599522_f_at
437
AA599522
squamous cell carcinoma antigen
−2.5
0.03100833






recognised by T cells


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



RC_AA219552_s_at
134
AA219552
ESTs
−2.5
0.043156485



RC_AA447537_at
350
AA447537
ESTs, Moderately similar to (define
−2.5
0.031129269






not available 5360237) [M. musculus]



RC_AA070752_s_at
51
AA070752
insulin receptor substrate 12q36
−2.5
0.002895462



RC_R02003_r_at
804
R02003
ESTs, Weakly similar to cappuccino
−2.4
0.002315115






[D. melanogaster]



L13698_at
638
L13698
growth arrest-specific 19q21.3-q22.1
−2.4
0.013393145



RC_AA432292_at
325
AA432292
ESTs, Moderately similar to B cell
−2.4
0.000956642






growth factor [H. sapiens ]



RC_H99648_s_at
613
H99648
DNA segment, single copy probe
−2.4
0.009066307






LNS-CAI/LNS-CAII (deleted in






polyposis5q22-q23



RC_AA131919_at
75
AA131919
putative type II membrane protein
−2.4
0.000187872



RC_AA621695_at
458
AA621695
ESTs
−2.4
0.008761556



RC_AA598695_at
427
AA598695
ESTs, Weakly similar to !!!! ALU
−2.4
0.000549977






SUBFAMILY SX WARNING ENTRY






!!!! [H. sapiens ]



RC_AA430388_at
321
AA430388
ESTs, Moderately similar to !!!! ALU
−2.4
0.000135176






SUBFAMILY SQ WARNING ENTRY






!!!! [H. sapiens ]



M24069_at
672
M24069
cold shock domain protein A12p13.1
−2.4
0.015890231



RC_AA434108_at
327
AA434108
Homo sapiens heat shock protein
−2.4
0.013182623






hsp40-3 mRNA, complete cds



RC_AA405488_at
268
AA405488
ESTs
−2.3
0.015044159



RC_AA419546_at
297
AA419546
ESTs
−2.3
0.030432017



RC_W38197_at

W38197
EST
−2.3
0.013006462



RC_R38709_s_at
824
R38709
superoxide dismutase 2,
−2.3
0.03567491






mitochondrial6q25.3



RC_AA121142_at
69
AA121142
ESTs, Moderately similar to copper
−2.3
0.043639016






transport protein HAH1 [H. sapiens ]



RC_N26801_at
730
N26801
ESTs
−2.3
0.000580867



RC_N75960_at
781
N75960
ESTs
−2.3
0.01244791



RC_R36969_at
820
R36969
ESTs
−2.3
0.019129486



AA046840_at
36
AA046840
CCAAT/enhancer binding protein
−2.3
0.002504544






(C/EBP), delta8p11.2-p11.1



RC_R46074_at
840
R46074
transforming, acidic coiled-coil
−2.3
0.003462273






containing protein 210q26



X06956_at
1051
X06956
tubulin, alpha 1 (testis specific)2q
−2.3
0.015437809



RC_H84761_s_at
599
H84761
glutathione peroxidase 13p21.3
−2.2
0.000365528



RC_W52065_f_at
1012
W52065
KIAA0539 gene product
−2.2
0.016497348



RC_AA279757_at
192
AA279757
ESTs, Weakly similar to (define not
−2.2
0.003272622






available 4481810) [D. melanogaster]



RC_H16676_s_at
556
H16676
ESTs, Weakly similar to (define not
−2.2
8.86866E−05






available 5107634) 8 R. norvegicus]



RC_AA255480_at
173
AA255480
ESTs
−2.2
0.009359024



RC_R96924_s_at
866
R96924
ESTs
−2.2
0.000201685



RC_AA342337_at
231
AA342337
ESTs, Moderately similar to !!!! ALU
−2.2
0.024999347






SUBFAMILY SQ WARNING ENTRY






!!!! [H. sapiens ]



RC_AA004699_at
1
AA004699
putative translation initiation factor
−2.2
0.022298405


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



RC_AA401965_at
258
AA401965
tumor suppressor deleted in oral
−2.2
0.006294885






cancer-related 111q13



RC_F02470_at
524
F02470
Homo sapiens clone 24796 mRNA
−2.2
0.022313149






sequence



X76180_at
1086
X76180
sodium channel, nonvoltage-gated 1
−2.2
0.023078001






alpha 12p13



RC_R49138_s_at
841
R49138
coatomer protein complex, subunit
−2.2
0.020401578






epsilon



RC_D80237_s_at
506
D80237
actin related protein 2/3 complex,
−2.2
0.022022634






subunit 4 (20 kD)



RC_AA402224_at
260
AA402224
growth arrest and DNA-damage-
−2.2
0.014983528






inducible, gamma9q22.1-q22.2



RC_AA281599_at
203
AA281599
Homo sapiens mRNA for for histone
−2.2
0.029567009






H2B, clone pjG4-5-14



RC_N78630_at
782
N78630
KIAA0870 protein
−2.2
0.006668895



X85785_rna1_at
1091
X85785
Duffy blood group1q21-q22
−2.2
0.018706507



RC_AA412063_at
285
AA412063
ESTs
−2.2
0.000686563



RC_AA022886_at
14
AA022886
ESTs, Weakly similar to
−2.2
0.000777067






phosphatidylinositol transfer protein






[H. sapiens ]



RC_N24899_at
726
N24899
ESTs
−2.2
0.030610964



RC_AA101767_at
66
AA101767
ESTs
−2.2
0.009040467



RC_AA045503_at
32
AA045503
ESTs, Weakly similar to Homo
−2.2
0.021950966






sapiens p20 protein [H. sapiens ]



RC_F10078_at
538
F10078
ESTs
−2.1
0.040699115



RC_H02308_at
545
H02308
ESTs
−2.1
0.036730715



RC_AA284153_at
210
AA284153
ESTs
−2.1
0.021270233



RC_AA453433_at
363
AA453433
HLA-B associated transcript-16p21.3
−2.1
0.013366375



RC_AA403159_at
265
AA403159
Homo sapiens Ste-20 related kinase
−2.1
0.025212073






SPAK mRNA, complete cds



RC_T17428_s_at
883
T17428
Homo sapiens clone 23836 mRNA
−2.1
0.044754602






sequence



RC_W92449_at
1037
W92449
ESTs, Highly similar to (defline not
−2.1
0.019386585






available 4587714) [H. sapiens ]



RC_AA609312_at
443
AA609312
ESTs
−2.1
0.003204911



D28589_at
486
D28589
Human mRNA (KIAA00167), partial
−2.1
0.000408478






sequence



RC_AA232508_at
139
AA232508
ESTs, Highly similar to (defline not
−2.1
0.004626663






available 4929647) [H. sapiens ]



RC_AA280929_5_at
199
AA280929
ESTs
−2.1
0.028189798



W63793_at
1020
W63793
S-adenosylmethionine decarboxylase
−2.1
0.032076011






16q21-q22



RC_R36881_s_at
819
R36881
Homo sapiens DNA from
−2.1
0.007343473






chromosome 19-cosmid R30879






containing USF2, genomic sequence



RC_AA278767_s_at
188
AA278767
ESTs
−2.1
0.001983494



RC_R98442_at
867
R98442
ESTs
−2.1
0.007227226



X99728_at
1098
X99728
H. sapiens NDUFV3 gene, exon 3.
−2.1
0.001404191



RC_R09379_at
807
R09379
solute carrier family 11 (proton-
−2.1
0.006004344






coupled divalent metal ion






transporters), member 212q13


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



RC_R99092_at
868
R99092
EST, Moderately similar to (define
−2.1
0.016256526






not available 5052951) [H. sapiens ]



X95325_s_at
1095
X95325
cold shock domain protein A12p13.1
−2.1
0.025953179



RC_T56281 f_at
902
T56281
Human metallothionein (MT)I-F gene
−2.1
0.032089569



RC_R44397_at
835
R44397
ESTs
−2.1
0.000265391



RC_H27180_f_at
568
H27180
ESTs
−2.1
0.004317675



AA165312_at
103
AA165312
ESTs
−2.1
0.025559572



RC_AA279313_s_at
191
AA279313
methyl CpG binding protein 2Xq28
−2.1
0.030594523



HG4322-HT4592_at
465
AF141349
Homo sapiens beta-tubulin mRNA,
−2.1
0.017120749






complete cds.



RC_H81413_f_at
597
H81413
high-mobility group (nonhistone
−2.1
0.009976588






chromosomal) protein isoforms I and






Y6p21



RC_W94333_at
1039
W94333
ESTs, Highly similar to (define not
−2.1
0.000435688






available 5107163) [H. sapiens ]



RC_AA455070_at
369
AA455070
eukaryotic translation initiation factor
−2.1
0.025226928






3, subunit 1 (alpha, 35kD)



RC_R11526_f_at
809
R11526
parathymosin17q12-q22
−2.1
0.027182202



RC_T15409_f_at
877
T15409
EST
−2.1
0.001478856



RC_H05625_f_at
548
H05625
ESTs
−2.1
0.024564209



RC_AA620461_at
452
AA620461
ESTs
−2.0
0.022844667



RC_AA449791_f_at
356
AA449791
EST
−2.0
0.025394324



RC_AA435769_s_at
330
AA435769
ESTs
−2.0
0.008375153



RC_N55502_at
755
N55502
ESTs
−2.0
0.021894439



AF001294_at
463
AF001294
tumor suppressing subtransferable
−2.0
0.03566128






candidate 311p15.5



RC_Z40898_at
1118
Z40898
ESTs, Highly similar to (defline not
−2.0
0.002289892






available 4929639) [H. sapiens ]



RC_AA436861_at
340
AA436861
ESTs
−2.0
0.00187676



M63573_at
697
M63573
peptidyiprolyl isomerase B
−2.0
0.044239663






(cyclophilin B)15



RC_T25732_f_at
888
T25732
KIAA0252 protein
−2.0
0.041237995



RC_R01257_at
803
R01257
ESTs, Weakly similar to (defline not
−2.0
0.005735841






available 4456991) [H. sapiens ]



RC_H91703_i_at
603
H91703
cell division cycle 2717q12-17q23.2
−2.0
0.001412925



RC_N34817_at
739
N34817
ESTs
−2.0
0.040996591



RC_R60777_at
850
R60777
ESTs, Weakly similar to KIAA0374
−2.0
0.000245565






[H. sapiens ]



RC_AA386264_at
245
AA386264
ESTs, Weakly similar to
−2.0
0.000541139






MICROTUBULE-ASSOCIATED






PROTEIN 1B [M. musculus]



RC_AA251769_at
168
AA251769
ESTs, Weakly similar to Containing
−2.0
0.008985897






ATP/GTP-binding site motif A(P-






loop): Similar to C. elegans






protein(P1:CEC47E128);Similar to






Mouse alpha-






mannosidase(P1:B54407)






[H. sapiens ]



RC_R56602_at
846
R56602
Ig superfamily proteinXq12-q13.3
−2.0
0.024051216



RC_AA397919_at
247
AA397919
ESTs
−2.0
0.029784087


Up-
RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for
22.5
0.025197485


regulated



Burkitt's lymphoma receptor-1)4q21



RC_W37778_f_at
1002
W37778
ESTs, Weakly similar to envelope
−2.0
0.043013942






protein [H. sapiens ]



AA248555_at
164
AA248555
ESTs
−2.0
0.000824698



RC_AA463693_at
385
AA463693
ESTs, Weakly similar to
−2.0
0.002809026






SERINE/THREONINE-PROTEIN






KINASE NEK3 [H. sapiens ]



W76181_at
1030
W76181
NADH dehydrogenase (ubiquinone) 1
−2.0
0.008370263






alpha subcomplex, 2 (8kD, B8)5q31



RC_AA171939_at
106
AA171939
ESTs
−2.0
0.015796116



U30999_at
961
U30999
U30999 Homo sapiens MV3
−2.0
0.007070546






melanoma Homo sapiens cDNA






clone memd



RC_F03254_f_at
527
F03254
synuclein, alpha (non A4 component
−2.0
0.011479379






of amyloid precursor)4q21



RC_H26288_at
567
H26288
ESTs, Weakly similar to !!!! ALU
−2.0
0.000262324






SUBFAMILY SC WARNING ENTRY






!!!! [H. sapiens ]



RC_AA007158_f_at
4
AA007158
ESTs
−2.0
0.001870921



RC_Z38785_at
1109
Z38785
Homo sapiens clone 23940 mRNA
−2.0
0.013437083






sequence



RC_AA282247_at
204
AA282247
ESTs
−2.0
0.000515617



RC_T23935_s_at
887
T23935
ESTs, Weakly similar to protein-
−2.0
0.006493804






tyrosine phosphatase [H. sapiens ]



RC_R59593_at
848
R59593
ESTs
−2.0
0.014592934



RC_AA446241_at
345
AA446241
tropomyosin 2 (beta)9p13.2-p13.1
−2.0
0.040680667



RC_Z40556_at
1116
Z40556
DJ222E13.1a.1 (C-terminal part of
−2.0
0.019444878






novel protein dJ222E13.1) (partial






isoform 1)



RC_AA159025_at
100
AA159025
ESTs, Highly similar to (defline not
−2.0
0.01375696






available 4680655) [H. sapiens ]



RC_H03387_s_at
546
H03387
estrogen-responsive B box
−2.0
0.036382844






protein17p11.2



RC_H17333_at
558
H17333
EST
−2.0
0.018111182



RC_AA412722_s_at
289
AA412722
putative cyclin G1 interacting
−2.0
0.006838915






protein7



U65579_at
979
U65579
NADH dehydrogenase (ubiquinone)
−2.0
0.013707565






Fe-S protein 8 (23 kD) (NADH-






coenzyme Q reductase)11q13



RC_R88209_at
860
R88209
ESTs
−2.0
0.040272012



RC_Z38266_at
1106
Z38266
Homo sapiens PAC clone
−2.0
0.009414008






DJ0777O23 from 7p14-p15
















TABLE 2







Normal1-Normal2 vs BPH-Cancer (Up-regulated)
















Fold-Change
p-value



SEQ ID


N1-N2 vs
N1-N2 vs


Affymetrix element
NO:
Genbank ID
Genbank Name
Cancer
Cancer















L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19c113.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog14q24.3


V01512_rnal_at
993
V01512
v-fos FBJ murine osteosarcoma viral oncogene
16.0
0.001216643





homolog14q24.3


RC_T90619_f_at
926
T90619
actin, gamma 117q25
15.7
0.044124187


U20734_s_at
952
U20734
jun B proto-oncogene19p13.2
14.3
0.004404553


U62015_at
978
U62015
insulin-like growth factor binding protein 101p22-
13.8
0.000487216





p31


AA374109_at
241
AA374109
ESTs, Moderately similar to (define not available
13.0
0.025911461





5031506) [R. norvegicus]


RC_T79768_at
914
T79768
ESTs
12.2
0.018940142


RC_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for Burkitt's
11.1
0.046025784





lymphoma receptor-1)4q21


X52541_at
1064
X52541
early growth response 15q31.1
9.7
0.003167537


RC_N66802_at
767
N66802
early growth response 38p23-p21
9.7
0.026764792


RC_AA463726_s_at
386
AA463726
JM27 proteinXp11.23
9.4
0.003409168


N40141_at
743
N40141
JM27 proteinXp11.23
8.4
0.021768214


M34996_s_at
685
M34996
major histocompatibility complex, class II, DQ
7.7
0.015886207





alpha 16p21.3


RC_T67053_f_at
909
T67053
immumoglobulin lambda gene cluster22q11.1-
7.4
0.000196865





q11.2


RC_AA404957_at
266
AA404957
ESTs, Highly similar to MATRIX GLA-PROTEIN
6.6
0.011451385





PRECURSOR [H. sapiens]


RC_H64493_f_at
590
H64493
immunoglobulin gamma 3 (Gm marker)14q32.33
6.5
0.002716347


RC_N47686_s_at
744
N47686
solute carrier family 14 (urea transporter), member
6.3
0.015568892





1 (Kidd blood group)18q11-q12


RC_W44760_s_at
1006
W44760
frizzled-related protein2qter
6.3
0.016891036


L19871_at
642
L19871
activating transcription factor 3
6.2
0.007603286


M92934_at
708
M92934
connective tissue growth factor6q23.1
6.1
0.001046931


M62831_at
695
M62831
immediate early protein19
5.8
0.00753286


L22524_s_at
643
L22524
matrix metalloproteinase 7 (matrilysin,
5.8
0.048289798





uterine)11q21-q22


J03507_at
621
J03507
complement component 75p13
5.6
0.00240657


RC_AA236455_r_at
153
AA236455
ESTs
5.5
0.022653542


RC_AA450127_at
359
AA450127
growth arrest and DNA-damage-inducible,
5.5
0.023227588





beta19p13.3


RC_AA281345_f_at
201
AA281345
immediate early protein19
5.4
0.003661068


RC_N30198_at
733
N30198
ESTs
5.3
0.005657756


AFFX-
1040
X00351
Human mRNA for beta-actin
5.3
0.01547291


HSAC07/X00351_5_at


D83018_at
513
D83018
nel (chicken)-like 212q13.11-q13.12
5.1
0.003774757


J04111_at
624
J04111
Jun activation domain binding protein1p32-p31
5.0
0.000243067


X51345_at
1062
X51345
jun B proto-oncogene19p13.2
5.0
0.017173421


RC_AA398903_at
250
AA398903
ESTs, Weakly similar to !!!! ALU SUBFAMILY J
4.9
0.014577818





WARNING ENTRY !!!! [H. sapiens]


RC_H17550_at
559
H17550
ESTs
4.7
0.012079391


S81914_at
873
S81914
immediate early response 36p21.3
4.5
0.006218653


RC_AA250958_f_at
167
AA250958
EST
4.4
1.88343E−05


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog14q24.3


RC_AA446651_at
346
AA446651
ESTs
4.4
0.026022802


HG1872-HT1907_at
674
M28590
Human (clone pcDG-79) MHC HLA-DG protein 41
4.3
0.008830524





mRNA, partial cds.


RC_AA490667_at
419
AA490667
ESTs
4.3
0.048863016


RC_N67041_at
768
N67041
ESTs
4.1
0.009333688


V00563_at
991
V00563
immunoglobulin mu14q32.33
4.1
0.004301939


X57809_s_at
1069
X57809
immumoglobulin lambda gene cluster22q11.1-
4.1
0.025371658





q11.2


R69417_at
852
R69417
ESTs
4.1
0.046373179


J00231_f_at
617
J00231
immunoglobulin gamma 3 (Gm marker)14q32.33
4.0
0.004766015


RC_AA402903_f_at
263
AA402903
immunoglobulin gamma 3 (Gm marker)14q32.33
3.9
0.000172905


U21128_at
953
U21128
lumican12q21.3-q22
3.9
0.000708917


M12529_at
655
M12529
apolipoprotein E19q13.2
3.7
0.026856247


RC_AA436616_at
335
AA436616
ESTs
3.7
0.020860083


U72649_at
983
U72649
B-cell translocation gene 2 (pheochromacytoma
3.7
0.002487396





cell-3)1q32


X03689_s_at
1044
X03689
Human mRNA fragment for elongation factor TU
3.7
0.04821902





(N-terminus)


AFFX-
1040
X00351
Human mRNA for beta-actin
3.6
0.029717275


HSAC07/X00351_5_at


RC_T62857_at
903
T62857
ESTs
3.6
0.002846539


Z74616_s_at
1123
Z74616
collagen, type I, alpha 27q22.1
3.6
0.004328291


X06700_s_at
1049
X06700
collagen, type III, alpha 1 (Ehlers-Danlos
3.6
0.010596098





syndrome type IV, autosomal dominant)2q31


RC_H86112_f_at
600
H86112
KIAA0471 gene product1q24-q25
3.6
0.017013968


M57466_s_at
690
M57466
major histocompatibility complex, class II, DP beta
3.5
0.005924671





16p2l.3


RC_F09281_at
533
F09281
ESTs
3.5
0.006841731


RC_R51831_at
843
R51831
ESTs
3.4
0.000941423


RC_H21814_f_at
563
H21814
immumoglobulin lambda gene cluster22q11.1-
3.4
0.009767098





q11.2


RC_W86513_at
1033
W86513
ESTs
3.4
0.003776481


RC_H40424_s_at
572
H40424
EST
3.4
0.016283906


X57025_at
1066
X57025
insulin-like growth factor 1 (somatomedin C)12q22
3.3
0.040489253





q23


RC_AA044219_at
29
AA044219
BK984G1.1 (PUTATIVE C-terminal end of a novel
3.3
0.001761114





protein with Collagen triple helix repeats)


RC_AA028092_s_at
17
AA028092
transcription factor 216pter-qter
3.3
0.003405482


RC_AA446661_at
347
AA446661
ESTs
3.3
0.041188995


RC_D80063_f_at
506
D80063
ESTs
3.3
0.049585142


M92843_s_at
707
M92843
zinc finger protein homologous to Zfp-36 in
3.3
0.006174082





mouse19q13.1


M34516_r_at
684
M34516
immunoglobulin lambda-like polypeptide 322q11.2
3.2
0.02344053


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog14q24.3


M87789_s_at
704
M87789
immunoglobulin gamma 3 (Gm marker)14q32.33
3.2
0.004534646


N75870_s_at
780
N75870
dual specificity phosphatase 15q34
3.2
0.000157434


RC_AA609309_at
442
AA609309
ESTs, Moderately similar to !!!!
3.1
0.03780658





ALU SUBFAMILY SB2 WARNING ENTRY !!!!





[H. sapiens]


S59049_at
870
S59049
regulator of G-protein signalling 11q31
3.0
0.002419303


AFFX-
679
M33197
Human GAPDH
3.0
0.034538288


HUMGAPDH/M33197_5_at


RC_D51060_s_at
495
D51060
Jun activation domain binding protein1p32-p31
3.0
0.022390037


RC_T23468_at
884
T23468
ESTs
2.9
0.001634616


U30521_at
960
U30521
P311 protein
2.9
0.009484198


Z48501_s_at
1121
Z48501
poly(A)-binding protein-like 13q22-q25
2.9
0.026396977


W73859_at
1028
W73859
transcription factor 216pter-qter
2.9
0.037326183


AA093923_at
63
AA093923
tissue inhibitor of metalloproteinase 217q25
2.8
0.041564022


RC_AA236476_at
154
AA236476
ESTs, Weakly similar to (defline not available
2.7
0.038305276





4507549) [H. sapiens]


U10550_at
944
U10550
GTP-binding protein overexpressed in skeletal
2.7
0.040657885





muscle8q13-q21


RC_N24902_at
727
N24902
E1B-55kDa-associated protein 5
2.7
0.03810507


RC_AA056121_at
46
AA056121
ESTs
2.7
0.024285705


RC_H98835_at
611
H98835
ESTs
2.7
0.019901442


K02405_f_at
629
K02405
Human MHC class II HLA-DQ-beta mRNA (DR7
2.7
0.00138806





DQw2), complete cds


U90552_s_at
988
U90552
butyrophilin, subfamily 3, member A16p23
2.7
3.91186E−05


RC_N59831_at
759
N59831
ESTs
2.7
0.04543669


L33799_at
645
L33799
procollagen C-endopeptidase enhancer7q22
2.7
0.010879277


RC_N59532_s_at
758
N59532
aminomethyltransferase (glycine cleavage system
2.6
0.025712285





protein T)3p21.2-p21.1


D13628_at
476
D13628
angiopoietin 16q22.3-q23
2.6
0.027204836


AA156897_s_at
97
AA156897
Homo sapiens mRNA; cDNA DKFZp564I1922
2.6
0.001580022





(from clone DKFZp564I1922)


RC_N67876_s_at
773
N67876
insulin-like growth factor 1 (somatomedin C)12q22
2.6
0.03992641





q23


M73720_at
702
M73720
carboxypeptidase A3 (mast cell)3q21-q25
2.6
0.023298997


H49440_at
578
H49440
nudix (nucleoside diphosphate linked moiety X)-
2.6
0.002498701





type motif 36p21.2


RC_AA250850_at
166
AA250850
adrenergic, beta, receptor kinase 222q11
2.5
0.041156086


RC_T49061_at
894
T49061
ESTs
2.5
0.00934004


W28214_at
996
W28214
ESTs
2.5
0.037677921


RC_H44631_s_at
573
H44631
immediate early protein19
2.5
0.0423037


D28137_at
484
D28137
bone marrow stromal cell antigen 219p13.2
2.5
0.026212334


RC_AA609027_at
441
AA609027
ESTs
2.5
0.038550623


RC_AA257093_r_at
178
AA257093
T-cell receptor, beta cluster7q35
2.4
0.002653232


RC_F13763_at
542
F13763
ESTs
2.4
0.016949277


RC_H08548_s_at
550
H08548
ATP citrate lyase17q12-q21
2.4
0.036998522


RC_AA436618_at
336
AA436618
ESTs
2.4
0.001789907


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog14q24.3


RC_W45664_s_at
1008
W456645
nucleotidase (CD73)6q14-q21
2.4
0.001762727


AA082546_at
54
AA082546
ESTs
2.4
0.021791878


D10522_at
471
010522
myristoylated alanine-rich protein kinase C
2.4
0.017333686





substrate (MARCKS, 80 K-L)6q22.2


RC_AA411860_at
280
AA411860
ESTs, Highly similar to (defline not available
2.4
0.02766922





4929723) [H. sapiens]


AB002340_at
461
AB002340
KIAA0342 gene product
2.3
0.003238699


U53445_at
972
U53445
downregulated in ovarian cancer 13
2.3
0.009361652


AA091278_at
60
AA091278
ESTs
2.3
0.046253689


RC_AA486072_i_at
410
AA486072
small inducible cytokine A5 (RANTES)17q11.2-
2.3
0.012816473





q12


RC_T53590_s_at
899
T53590
cytochrome P450, subfamily XIA (cholesterol side
2.3
4.29636E−05





chain cleavage)15q23-q24


RC_N91971_f_at
791
N91971
retinol-binding protein 1, cellular3q23
2.3
0.025171598


RC_AA043777_at
28
AA043777
ESTs
2.3
0.004490188


RC_H54764_at
580
H54764
EST, Weakly similar to X-linked retinopathy
2.3
0.036980431





protein {C-terminal, clone XEH.8c} [H. sapiens]


RC_AA443923_at
344
AA443923
ESTs
2.3
0.025833241


U60975_at
977
U60975
Homo sapiens gp250 precursor, mRNA, complete
2.3
0.041238204





cds.


M34516_at
684
M34516
immunoglobulin lambda-like polypeptide 322q11.2
2.3
0.041388637


RC_N36001_at
740
N36001
ESTs, Weakly similar to !!!! ALU CLASS C
2.2
0.000449076





WARNING ENTRY !!!! [H. sapiens]


AF010193_at
464
AF010193
MAD (mothers against decapentaplegic,
2.2
0.005397771





Drosophila) homolog 718


AFFX-
1040
X00351
Human mRNA for beta-actin
2.2
0.037852217


HSAC07/X00351_5_at


RC_AA158262_s_at
99
AA158262
calpastatin5q14–q22
2.2
0.006648962


RC_AA156565_at
96
AA156565
4-nitrophenylphosphatase domain and non-
2.2
0.020901922





neuronal SNAP25-like 122q12


Z11793_at
1104
Z11793
selenoprotein P, plasma, 15q31
2.2
0.00118281


RC_D80059_s_at
504
D80059
ESTs
2.2
0.033534432


RC_AA450324_at
360
AA450324
ESTs
2.2
0.024832006


RC_N39415_at
742
N39415
osteoglycin (osteoinductive factor)
2.2
0.032001116


RC_T23622_at
886
T23622
ESTs
2.2
0.040417825


RC_AA599365_at
434
AA599365
decorin12q23
2.2
0.011325181


X62320_at
1073
X62320
granulin17
2.2
0.043043858


RC_R85291_at
859
R85291
ESTs
2.2
0.004987693


M11313_s_at
654
M11313
alpha-2-macroglobulin12p13.3-p12.3
2.2
0.011545737


AA047151_at
37
AA047151
ESTs
2.2
0.033987576


RC_AA205724_at
123
AA205724
ESTs
2.2
0.004569368


RC_AA086264_i_at
59
AA086264
ESTs, Highly similar to (defline not available
2.2
0.020637423





4191348) [H. sapiens]


RC_R42424_at
832
R42424
ESTs
2.2
0.033603417


RC_AA347359_s_at
233
AA347359
lysozyme (renal amyloidosis)12
2.1
0.028764499


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog14q24.3


AA092716_at
62
AA092716
HLA-B associated transcript-36p21.3
2.1
0.031717351


RC_R42241_at
830
R42241
ESTs
2.1
0.008013968


RC_N57577_at
756
N57577
KIAA0663 gene product
2.1
0.032028875


RC_W67577_s_at
1022
W67577
CD74 antigen (invariant polypeptide of major
2.1
0.002072118





histocompatibility complex, class II antigen-





associated)5q32


C02016_at
466
C02016
KIAA0447 gene product
2.1
0.002399894


RC_AA256268_at
175
AA256268
ESTs
2.1
0.0269568


RC_T96171_at
930
T96171
EST
2.1
0.012219229


X72841_at
1083
X72841
retinoblastoma-binding protein 7
2.1
0.033774692


RC_R45698_at
839
R45698
ESTs
2.1
0.049975895


RC_N22006_s_at
719
N22006
EST
2.1
0.011131338


RC_N69222_at
777
N69222
ESTs
2.1
0.022256915


RC_H97538_at
607
H97538
ESTs
2.0
0.03795259


RC_AA039935_at
23
AA039935
dynein light chain, outer arm 422q12.3–q13.2
2.0
0.011488766


RC_AA084138_at
55
AA084138
ESTs
2.0
0.011124432


AB002379_at
462
AB002379
KIAA0381 protein
2.0
0.000530413


RC_AA460651_at
379
AA460651
heterogeneous nuclear protein similar to rat helix
2.0
0.027697892





destabilizing protein10


RC_W02204_at
994
W02204
solute carrier family 24
2.0
0.00115779





(sodium/potassium/calcium exchanger), member





115q22


Y08614_at
1101
Y08614
exportin 1 (CRM1, yeast, homolog)2p16
2.0
0.035368368


D31134_at
488
D31134
KIAA1075 protein
2.0
0.021196526


M94880_f_at
711
M94880
major histocompatibility complex, class I, A6p21.3
2.0
0.025382167


J03040_at
619
J03040
secreted protein, acidic, cysteine-rich
2.0
0.035472553





(osteonectin)5q31.3-q32


RC_N68350_at
775
N68350
ESTs
2.0
0.042917893


RC_H48793_at
577
H48793
EST
2.0
0.00296551


HG3543-HT3739_at
675
M29645
insulin-like growth factor 2 (somatomedin
2.0
0.019712374





A)11p15.5


RC_W33172_at
999
W33172
ESTs, Weakly similar to ORF2 [M. musculus]
2.0
0.006454106


RC_R08850_at
806
R08850
ESTs
2.0
0.011364766


W52638_at
1014
W52638
ESTs
2.0
0.010612401


M19045_f_at
662
M19045
lysozyme (renal amyloidosis)12
2.0
0.004561974


RC_AA312946_s_at
228
AA312946
ESTs
2.0
0.020272205


RC_AA235310_at
148
AA235310
ESTs
2.0
0.011954937


X03100_cds2_at
1043
X03100
Human mRNA for SB classII histocompatibility
2.0
0.002404541





antigen alpha-chain


RC_T16282_f_at
881
T16282
wee1 + (S. pombe)homolog11p15.3-p15.1
2.0
0.031472155


RC_H66642_f_at
591
H66642
ESTs, Moderately similar to !!!!
2.0
0.02460529





ALU SUBFAMILY SQ WARNING ENTRY !!!!





[H. sapiens]


RC_AA342337_at
231
AA342337
ESTs, Moderately similar to !!!!
−23.7
3.26344E−05





ALU SUBFAMILY SQ WARNING ENTRY !!!!





[H. sapiens]


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog14q24.3


RC_AA398908_at
251
AA398908
Human Chromosome 16 BAC clone CIT987SK-A-
−21.7
0.040053626





61E3


RC_H15143_s_at
554
H15143
Human clone 23575 mRNA, partial cds
−13.8
0.028261625


RC_N80129_i_at
785
N80129
metallothionein 1L16q13
−12.6
0.002146038


RC_AA465394_at
390
AA465394
ESTs
−12.6
0.004961162


RC_AA236545_at
156
AA236545
ESTs
−12.5
0.034938167


RC_W42778_at
1004
W42778
Homo sapiens clone 24636 mRNA sequence
−12.3
0.010449419


RC_T40895_at
892
T40895
ESTs
−12.0
0.01968535


RC_H94475_s_at
605
H94475
alpha-2-plasmin inhibitor17pter-p12
−11.7
0.012919819


RC_R71792_s_at
855
R71792
ESTs, Moderately similar to FAT-SPECIFIC
−10.4
0.002540356





PROTEIN FSP27 [M. musculus]


RC_AA609006_at
440
AA609006
ESTs
−7.5
0.013902978


RC_AA026641_s_at
16
AA026641
secretory leukocyte protease inhibitor
−7.0
0.01850877





(antileukoproteinase)


X65614_at
1076
X65614
S100 calcium-binding protein P4p16
−6.7
0.005634308


X93036_at
1093
X93036
phospholemman-like, expressed in breast tumors,
−6.6
0.005278275





8 kD


RC_T94447_s_at
928
T94447
ESTs, Moderately similar to (defline not available
−5.7
0.006891909





4335935) [M. musculus]


RC_AA405488_at
268
AA405488
ESTs
−5.5
0.00023986


RC_T73433_s_at
912
T73433
angiotensinogen1q41-qter
−5.5
0.009418205


M99487_at
716
M99487
folate hydrolase (prostate-specific membrane
−5.3
0.008067789





antigen) 111p11.2


RC_W88568_at
1035
W88568
glycogenin 2Xp22.3
−5.1
0.024739084


RC_AA460914_at
380
AA460914
ESTs
−5.0
0.024385552


X57129_at
1067
X57129
H1 histone family, member 26p21.3
−4.8
0.006322499


RC_Z41642_at
1119
Z41642
ESTs
−4.7
0.009525521


RC_R46074_at
840
R46074
transforming, acidic coiled-coil containing protein
−4.7
0.001327844





210q26


J03910_rna1_at
622
J03910
metallothionein 1G16q13
−4.6
0.004574277


RC_AA350265_at
237
AA350265
histone deacetylase A
−4.5
0.002897414


AA165312_at
103
AA165312
ESTs
−4.2
0.005487803


RC_AA419011_at
296
AA419011
Homo sapiens mRNA; cDNA DKFZp586D0823
−4.0
0.019079557





(from clone DKFZp58600823)


RC_N92502_s_at
794
N92502
ESTs, Moderately similar to HERV-E integrase
−4.0
0.030144039





[H. sapiens]


RC_F03969_at
528
F03969
ESTs, Weakly similar to tumorous imaginal discs
−4.0
0.017024613





protein Tid56 homolog [H. sapiens]


X76717_at
1087
X76717
metallothionein 1L16q13
−3.9
0.001145402


RC_AA416762_s_at
291
AA416762
nuclear receptor subfamily 1, group H, member
−3.8
0.011735303





219q13.3-19q13.3


RC_AA053424_at
40
AA053424
ESTs, Weakly similar to mucin Muc3
−3.8
0.009737433





[R. norvegicus]


X64177_f_at
1075
X64177
metallothionein 1H16q13
−3.7
0.003297195


RC_N32748_at
736
N32748
ESTs
−3.6
0.021454174


RC_AA416685_at
290
AA416685
UNC13 (C. elegans)-like9p11-p12
−3.6
0.016338392


RC_AA505136_at
426
AA505136
ESTs
−3.5
0.007200396


RC_AA165313_at
104
AA165313
ESTs
−3.5
0.037649191


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog14q24.3


RCF02245_at
522
F02245
monoamine oxidase AXp11.4-p11.3
−3.4
0.005486135


RC_AA004699_at
1
AA004699
putative translation initiation factor
−3.4
0.00057505


RC_AA599331_at
433
AA599331
ESTs
−3.4
0.01136457


RC_N26904_at
731
N26904
ESTs, Weakly similar to FK506/rapamycin-binding
−3.3
0.045410608





protein FKBP13 precursor [H. sapiens]


RC_AA070752_s_at
51
AA070752
insulin receptor substrate 12q36
−3.3
0.028433761


RC_AA599522_f_at
437
AA599522
squamous cell carcinoma antigen recognised by
−3.2
0.005311305





T cells


RC_N94303_at
797
N94303
ESTs
−3.1
0.000160723


RC_F10078_at
538
F10078
ESTs
−3.1
0.022464594


RC_AA447537_at
350
AA447537
ESTs, Moderately similar to (defline not available
−3.1
0.007323728





5360237) [M. musculus]


L77701_at
651
L77701
human homolog of yeast mitochondrial copper
−3.0
0.001489928





recruitment gene


RC_H27675_at
569
H27675
ESTs
−3.0
0.016160504


V00594_at
992
V00594
metallothionein 2A16q13
−2.9
0.001495259


U52969_at
970
U52969
Purkinje cell protein 421q22.2-q22.3
−2.9
6.3447E−05


RC_R42607_at
834
R42607
ESTs
−2.8
0.008960052


RC_AA451836_at
362
AA451836
ESTs
−2.7
0.008401586


RC_F04492_at
531
F04492
ESTs, Weakly similar to !!!! ALU SUBFAMILY J
−2.7
0.001443051





WARNING ENTRY !!!! [H. sapiens]


RC_H77597_f_at
594
H77597
metallothionein 1H16q13
−2.7
0.00332868


RC_AA430388_at
321
AA430388
ESTs, Moderately similar to !!!!
−2.7
0.000114004





ALU SUBFAMILY SQ WARNING ENTRY !!!!





[H. sapiens]


RC_T90190_s_at
925
T90190
H1 histone family, member 26p21.3
−2.7
0.030242714


RC_H16171_f_at
555
H16171
cleft lip and palate associated transmembrane
−2.7
0.023414443





protein 119q13.2-q13.3


RC_AA022886_at
14
AA022886
ESTs, Weakly similar to phosphatidylinositol
−2.7
0.00489294





transfer protein [H. sapiens]


RC_R28370_at
815
R28370
ESTs
−2.7
0.003724547


RC_AA261907_at
182
AA261907
ESTs, Weakly similar to (define not available
−2.6
0.043689441





3874144) [C. elegans]


RC_W37778_f_at
1002
W37778
ESTs, Weakly similar to envelope protein
−2.6
0.030756837





[H. sapiens]


RC_T98019_at
932
T98019
EST, Highly similar to PEREGRIN [H. sapiens]
−2.5
0.035566681


RC_N33927_s_at
737
N33927
H2B histone family, member B6p21.3
−2.5
0.013093926


RC_R40431_at
828
R40431
Homo sapiens mRNA; cDNA DKFZp564D016
−2.5
0.004235538





(from clone DKFZp564D016)


RC_AA133756_at
78
AA133756
Rho-associated, coiled-coil containing protein
−2.5
0.012389163





kinase 22p24


RC_AA152200_s_at
92
AA152200
ESTs
−2.5
0.004366137


W63793_at
1020
W63793
S-adenosylmethionine decarboxylase 16q21-q22
−2.5
0.005714247


RC_AA410298_at
274
AA410298
ESTs
−2.5
0.018744617


X99728_at
1098
X99728
H. sapiens NDUFV3 gene, exon 3
−2.5
0.004580383


RC_W78127_at
1031
W78127
ESTs, Weakly similar to KIAA0425 [H. sapiens]
−2.5
0.001240164


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog 819q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog14q24.3


RC_R96924_a_at
866
R96924
ESTs
−2.5
0.006515911


RC_H16768_at
557
H16768
ESTs
−2.5
0.005669237


X76180_at
1086
X76180
sodium channel, nonvoltage-gated 1 alpha12p13
−2.5
0.007625025


RC_AA432162_at
324
AA432162
Homo sapiens mRNA; cDNA DKFZp58682022
−2.4
0.010199113





(from clone DKFZp586B2022)


RC_H88798_at
602
H88798
ESTs
−2.4
0.000783143


RC_AA609312_at
443
AA609312
ESTs
−2.4
0.016243321


RC_AA131919_at
75
AA131919
putative type II membrane protein
−2.4
0.000264791


RC_N80129_f_at
785
N80129
metallothionein 1L16q13
−2.4
0.002297016


RC_AA182030_at
110
AA182030
ESTs
−2.4
0.041632378


W70167_at
1025
W70167
ESTs
−2.4
0.00395969


RC_AA599522_r_at
437
AA599522
squamous cell carcinoma antigen recognised by T
−2.4
0.004347078





cells


RC_N52254_s_at
749
N52254
SH3-binding domain glutamic acid-rich
−2.4
0.011171389





protein21q22.3


RC_N95495_at
799
N95495
small inducible cytokine A5 (RANTES)17q11.2-
−2.4
0.002430242





q12


RC_T68873_f_at
911
T68873
metallothionein 1L16q13
−2.4
0.00320019


AA429539_f_at
318
AA429539
ESTs
−2.4
0.020751882


RC_AA435769_s_at
330
AA435769
ESTs
−2.4
0.009832353


RC_AA029356_at
18
AA029356
ESTs
−2.3
0.007208722


AA316686_s_at
229
AA316686
ESTs, Highly similar to huntingtin interacting
−2.3
0.000225753





protein HYPK [H. sapiens]


RC_H02308_at
545
H02308
ESTs
−2.3
0.041776289


RC_AA258476_at
179
AA258476
Homo sapiens mRNA; cDNA DKFZp564J0323
−2.3
0.02070961





(from clone DKFZp564J0323)


X06956_at
1051
X06956
tubulin, alpha 1 (testis specific)2q
−2.3
0.003656874


RC_H99694_at
614
H99694
ESTs
−2.3
0.013645335


RC_AA479044_s_at
402
AA479044
ESTs, Weakly similar to PROGASTRICSIN
−2.3
0.047032301





PRECURSOR [H. sapiens]


RC_AA436861_at
340
AA436861
ESTs
−2.3
0.001794201


M24069_at
672
M24069
cold shock domain protein A12p13.1
−2.3
0.014123514


RC_AA410311_at
275
AA410311
ESTs
−2.3
0.045227011


W52858_at
1015
W52858
Homo sapiens mRNA; cDNA DKFZp564F0522
−2.3
0.002276405





(from clone DKFZp564F0522)


RC_W38197_at

W38197
EST
−2.3
1.96016E−05


J00073_at
615
J00073
actin, alpha, cardiac muscle15q11-qter
−2.3
0.018476889


RC_D51069_f_at
496
D51069
melanoma adhesion molecule
−2.3
0.042693395


RC_AA504805_s_at
424
AA504805
interferon stimulated gene (20 kD)15q26
−2.3
0.008805886


RC_F03254_f_at
527
F03254
synuclein, alpha (non A4 component of amyloid
−2.3
0.003668915





precursor)4q21


M35252_at
686
M35252
tranamembrane 4 superfamily member 3
−2.3
0.028083185


RC_AA040731_at
25
AA040731
ESTs
−2.2
0.028924808


RC_AA496247_at
422
AA496247
ESTs
−2.2
0.013336314


X59766_at
1071
X59766
alpha-2-glycoprotein 1, zinc 7
−2.2
0.002003511


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog14q24.3


RC_R84421_at
857
R84421
eukaryotic translation elongation factor 1 alpha
−2.2
0.016333706





16q14


AA328993_s_at
230
AA328993
ESTs
−2.2
0.004438605


RC_R44535_f_at
836
R44535
endonuclease G9q34.1
−2.2
0.014319616


U41518_at
964
U41518
aquaporin 1 (channel-forming integral protein,
−2.2
0.009447457





28 kD)7p14


RC_W33179_at
1000
W33179
testis-specific kinase 21p32
−2.2
0.001104272


RC_H58873_s_at
583
H58873
solute carrier family 2 (facilitated glucose
−2.2
0.000238641





transporter), member 11p35-p31.3


RC_R31679_s_at
816
R31679
ESTs
−2.2
0.01000414


RC_AA189083_at
114
AA189083
ESTs, Highly similar to (defline not available
−2.2
0.002468046





4589468) [M. musculus]


RC_AA251769_at
168
AA251769
ESTs, Weakly similar to Containing ATP/GTP-
−2.2
0.010819016





binding site motif A(P-loop): Similar to C. elegans





protein(P1:CEC47E128); Similar to Mouse alpha-





mannosidase(P1:B54407) [H. sapiens]


RC_W70131_at
1024
W70131
ESTs
−2.2
0.02955725


RC_R09379_at
807
R09379
solute carrier family 11 (proton-coupled divalent
−2.2
0.009730513





metal ion transporters), member 212q13


RC_AA621695_at
458
AA621695
ESTs
−2.1
0.001994051


RC_H18947_at
561
H18947
ESTs
−2.1
0.027246274


RC_AA219552_s_at
134
AA219552
ESTs
−2.1
0.046510941


RC_N22620_at
722
N22620
ESTs
−2.1
0.013527392


RC_R02003_r_at
804
R02003
ESTs, Weakly similar to cappuccino
−2.1
0.010597095





[D. melanogaster]


RC_AA405559_at
270
AA405559
ESTs
−2.1
0.009305601


RC_AA463693_at
385
AA463693
ESTs, Weakly similar to SERINE/THREONINE-
−2.1
0.004156996





PROTEIN KINASE NEK3 [H. sapiens]


RC_AA481407_at
405
AA481407
ESTs
−2.1
0.002741696


M11119_at
653
M11119
Human endogenous retrovirus envelope region
−2.1
0.003718876





mRNA (PL1)


RC_AA159025_at
100
AA159025
ESTs, Highly similar to (defline not available
−2.1
0.011127532





4680655) [H. sapiens]


RC_AA411981_at
283
AA411981
ESTs, Weakly similar to putative seven pass
−2.1
0.044294612





transmembrane protein [H. sapiens]


RC_W57931_at
1017
W57931
ESTs, Moderately similar to CATHEPSIN D
−2.1
0.000755739





PRECURSOR [H. sapiens]


X66899_at
1081
X66899
Ewing sarcoma breakpoint region 122q12
−2.1
0.002068901


RC_R49327_at
842
R49327
solute carrier family 11 (proton-coupled divalent
−2.1
0.030928835





metal ion transporters), member 212q13


RC_AA609645_at
445
AA609645
eukaryotic translation initiation factor 4 gamma,
−2.1
0.04955957





13q27-qter


RC_AA434108_at
327
AA434108
Homo sapiens heat shock protein hsp40-3 mRNA,
−2.1
0.034468752





complete cds


X17567_s_at
1061
X17567
small nuclear ribonucleoprotein polypeptides B
−2.1
0.014475221





and B120


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog 14q24.3


J04164_at
626
J04164
interferon-induced protein 17
−2.1
0.023410352


RC_AA135929_s_at
80
AA135929
ESTs, Highly similar to (defline not available
−2.1
0.003009065





4103057) [M. musculus]


L04270_at
634
L04270
lymphotoxin beta receptor (TNFR superfamily,
−2.1
0.006776988





member 312p13


RC_H99035_at
612
H99035
ESTs
−2.1
0.001053584


M64673_at
698
M64673
heat shock transcription factor 1
−2.1
0.004283001


X85785_rna1_at
1091
X85785
Duffy blood group1q21-q22
−2.1
0.00657464


M68864_at
700
M68864
Human ORF mRNA, complete cds
−2.1
0.010185833


D50928_at
494
D50928
KIAA0138 gene product
−2.1
0.002283064


RC_AA282247_at
204
AA282247
ESTs
−2.0
0.007970044


RC_R00144_at
801
R00144
ESTs
−2.0
0.006939854


RC_AA485965_at
409
AA485965
ESTs, Highly similar to (defline not available
−2.0
0.000405037





4336766) [H. sapiens]


S45630_at
869
S45630
crystallin, alpha B11q22.3-q23.1
−2.0
0.006157273


RC_T89703_at
923
T89703
ESTs, Highly similar to (defline not available
−2.0
0.000286616





4455129) [H. sapiens]


RC_Z38785_at
1109
Z38785
Homo sapiens clone 23940 mRNA sequence
−2.0
0.00706437


X85373_at
1090
X85373
small nuclear ribonucleoprotein polypeptide G
−2.0
6.93881E−05


RC_F04816_at
532
F04816
ESTs
−2.0
0.005353184


RC_AA043349_at
27
AA043349
ESTs
−2.0
0.01749596


RC_H84761_s_at
599
H84761
glutathione peroxidase 13p21.3
−2.0
0.000116621


M34338_s_at
683
M34338
spermidine synthase1p36-p22
−2.0
0.008566137


L13698_at
638
L13698
growth arrest-specific 19q21.3-q22.1
−2.0
0.016504513


RC_N75960_at
781
N75960
ESTs
−2.0
0.024082428


D45370_at
491
D45370
adipose specific 210
−2.0
0.034362163


RC_AA401965_at
258
AA401965
tumor suppressor deleted in oral cancer-related
−2.0
0.011190087





111q13


RC_F09315_at
534
F09315
discs, large (Drosophila) homolog 510q23
−2.0
0.020753036


RC_AA025370_at
15
AA025370
KIAA0872 protein
−2.0
0.026565555


RC_H52835_at
579
H52835
phytanoyl-CoA hydroxylase (Refsum
−2.0
0.015021251





disease)10pter-p11.2


RC_H99648_s_at
613
H99648
DNA segment, single copy probe LNS-CAI/LNS-
−2.0
0.012115852





CAII (deleted in polyposis5q22-q23


RC_AA430074_at
320
AA430074
ESTs
−2.0
0.002355049


RC_AA598939_at
428
AA598939
ESTs
−2.0
0.011383872


AA455001_s_at
368
AA455001
ESTs
−2.0
0.000176199


RC_F09684_at
535
F09684
ESTs
−2.0
0.002741682


D42073_at
490
D42073
reticulocalbin 1, EF-hand calcium binding
−2.0
0.012881688





domain11p13


RC_AA598695_at
427
AA598695
ESTs, Weakly similar to !!!!
−2.0
4.77268E−06





ALU SUBFAMILY SX WARNING ENTRY !!!!





[H. sapiens]


D23662_at
481
D23662
neural precursor cell expressed, developmentally
−2.0
0.003156141





down-regulated 8


RC_AA431470_at
323
AA431470
proteinkinase (cAMP-dependent, catalytic)
−2.0
0.038692982





inhibitor gamma20q


RC_AA399273_at
253
AA399273
ESTs
−2.0
0.029403118


RC_AA142858_at
82
AA142858
ESTs
−2.0
0.00197166


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
18.8
0.03580379





homolog B19q13.3


RC_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
16.5
8.98673E−05





homolog B4q24.3


RC_Z40715_at
1117
Z40715
Homo sapiens mRNA; cDNA DKFZp586C201
−2.0
0.017206338





(from clone DKFZp586C201)


RC_AA490341_s_at
417
AA490341
ESTs
−2.0
0.004570941


RC_N67815_f_at
772
N67815
ESTs, Weakly similar to (defline not available
−2.0
0.002996692





4660655) [H. sapiens]


RC_N53359_at
750
N53359
ESTs
−2.0
0.034916164
















TABLE 3







Normal vs. BPH W/Symptoms (Up-regulated)













SEQ ID


Fold-



Affymetrix element
NO:
GenBank ID
GenBank Name
change
t















N40141_at
743
N40141
JM27 protein
17.4
−7.64


rc_N23730_s_at
724
N23730
v-fos FBJ murine osteosarcoma viral oncogene
10.8
−7.54





homolog


rc_AA463726_s_at
386
AA463726
JM27 protein
10.0
−6.56


rc_N23352_s_at
723
N23352
proenkephalin
10.0
−4.53


rc_H64493_f_at
590
H64493
immunoglobulin heavy constant gamma 3 (G3m
9.1
−4.36





marker)


V01512_rna1_at
993
V01512
v-fos FBJ murine osteosarcoma viral oncogene
9.1
−7.40





homolog


rc_H05704_r_at
549
H05704
HCR (a-helix coiled-coil rod homologue)
8.1
−2.79


L49169_at
649
L49169
FBJ murine osteosarcoma viral oncogene
8.0
−5.81





homolog B


rc_AA410383_at
277
AA410383
B-cell-homing chemokine (ligand for Burkitt's
7.5
−3.95





lymphoma receptor-1)


rc_AA131322_s_at
74
AA131322
tryptase, alpha,tryptase, beta (tryptase II)
7.2
−2.81


R56183_s_at
844
R56183
eukaryotic translation initiation factor 3, subunit 6
6.9
−2.77





(48 kD)


rc_AA461300_at
381
AA461300
ESTs
6.9
−7.08


J00231_f_at
617
J00231
immunoglobulin heavy constant gamma 3 (G3m
6.7
−4.62





marker)


rc_AA427622_s_at
311
AA427622
collagen, type XIII, alpha 1
6.6
−8.25


rc_T90889_at
927
T90889
ESTs
5.6
−3.72


rc_AA402903_f_at
263
AA402903
immunoglobulin heavy constant gamma 3 (G3m
5.6
−3.61





marker)


rc_T23622_at
886
T23622
ESTs
5.5
−5.24


rc_T62857_at
903
T62857
ESTs
5.4
−7.85


rc_AA256268_at
175
AA256268
ESTs
5.3
−6.86


rc_R44714_s_at
837
R44714
ESTs
5.3
−4.83


rc_AA236476_at
154
AA236476
transmembrane protein TENB2,
5.1
−3.13


rc_AA028092_s_at
17
AA028092
transcription factor 21
5.1
−5.24


rc_T90619_f_at
926
T90619
actin, gamma 1
5.0
−2.19


J00123_at
616
J00123
proenkephalin
5.0
−3.96


X52541_at
1064
X52541
early growth response 1
4.9
−5.78


rc_AA620825_at
454
AA620825
CGI-43 protein
4.9
−4.59


rc_AA424530_s_at
304
AA424530
ESTs
4.9
−5.42


rc_AA386386_s_at
246
AA386386
procollagen-proline, 2-oxoglutarate 4-
4.9
−2.64





dioxygenase (proline 4-hydroxylase), beta





polypeptide (protein disulfide isomerase; thyroid





hormone binding protein p55)


U62015_at
978
U62015
cysteine-rich, angiogenic inducer, 61
4.9
−6.24


rc_AA188981_at
112
AA188981
highly expressed in cancer, rich in leucine
4.9
−6.67





heptad repeats


rc_H21814_f_at
563
H21814
immunoglobulin lambda locus
4.9
−2.67


M60314_at
692
M60314
bone morphogenetic protein 5
4.7
−10.82


rc_T67053_f_at
909
T67053
immunoglobulin lambda locus
4.7
−2.84


rc_N47686_s_at
744
N47686
solute carrier family 14 (urea transporter),
4.7
−3.27





member 1 (Kidd blood group)


rc_AA436616_at
335
AA436616
ESTs
4.7
−6.34


rc_H60595_s_at
585
H60595
progesterone binding protein
4.7
−2.66


rc_H88338_at
601
H88338
ESTs
4.7
−7.93


M33653_at
682
M33653
collagen, type XIII, alpha 1
4.6
−8.95


rc_N30198_at
733
N30198
ESTs
4.5
−5.87


D83018_at
513
D83018
nel (chicken)-like 2
4.5
−9.79


rc_Z39904_at
1111
Z39904
ESTs
4.5
−6.27


H61295_s_at
586
H61295
CD4 antigen (p55)
4.4
−4.49


rc_AA281345_f_at
201
AA281345
immediate early protein
4.3
−6.62


rc_T23490_s_at
885
T23490
hypothetical protein FLJ20185
4.2
−5.25


rc_AA279760_at
193
AA279760
DKFZP564M182 protein
4.2
−3.73


rc_R25410_at
814
R25410
ESTs
4.2
−4.69


rc_T03229_f_at
874
T03229
ESTs
4.2
−3.37


rc_R93908_at
865
R93908
ESTs
4.2
−3.39


AA374109_at
241
AA374109
spondin 2, extracellular matrix protein
4.2
−1.97


rc_R45654_at
838
R45654
collagen, type XIII, alpha 1
4.2
−5.69


rc_H86112_f_at
600
H86112
KIAA0471 gene product
4.1
−4.00


rc_AA257093_r_at
178
AA257093
T cell receptor beta locus
4.1
−7.77


rc_AA456147_at
371
AA456147
general transcription factor IIIA
4.1
−6.23


U21128_at
953
U21128
lumican
4.1
−6.15


rc_AA057195_at
47
AA057195
TNF? elastin microfibril interface located protein
4.1
−2.22


M63438_s_at
696
M63438
immunoglobulin kappa variable 1D-8
4.0
−2.53


M57466_s_at
690
M57466
major histocompatibility complex, class II, DP
4.0
−3.91





beta 1


rc_AA443923_at
344
AA443923
cat eye syndrome critical region gene 1
4.0
−3.01


rc_N39415_at
742
N39415
DKFZP586P2421 protein
4.0
−5.70


rc_W67225_at
1021
W67225
KIAA0592 protein
4.0
−3.35


M62831_at
695
M62831
immediate early protein
4.0
−6.39


rc_AA404957_at
266
AA404957
matrix Gla protein
4.0
−3.84


rc_F02992_at
526
F02992
ESTs
4.0
−3.65


U69263_at
982
U69263
matrilin 2
3.9
−4.84


rc_AA448625_at
354
AA448625
slit (Drosophila) homolog 3
3.9
−4.13


X57025_at
1066
X57025
insulin-like growth factor 1 (somatomedin C)
3.9
−3.93


AA151544_at
91
AA151544
matrix metalloproteinase 23B
3.8
−5.54


rc_F13763_at
542
F13763
ESTs
3.8
−6.39


rc_AA436655_at
337
AA436655
hypothetical protein FLJ10781
3.8
−5.13


M87789_s_at
704
M87789
immunoglobulin heavy constant gamma 3 (G3m
3.8
−3.93





marker)


L44416_at
647
L44416
DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide
3.8
−1.75





17 (72 kD)


U20350_at
951
U20350
chemokine (C-X3-C) receptor 1
3.8
−6.50


rc_AA449749_at
355
AA449749
ESTs
3.8
−4.52


rc W73790_f_at
1027
W73790
immunoglobulin lambda-like polypeptide 1
3.7
−2.95


rc_AA281145_at
200
AA281145
ESTs
3.7
−1.77


rc_F09748_s_at
536
F09748
ESTs
3.7
−4.12


rc_T64211_at
906
T64211
HNOEL-iso protein
3.7
−5.35


rc_N80152_at
786
N80152
RNA binding motif protein 6
3.7
−2.40


rc_AA436618_at
336
AA436618
microtubule-associated protein 2
3.7
−4.67


T85532_f_at
917
T85532
ESTs
3.7
−1.90


rc_AA398280_at
248
AA398280
ESTs
3.6
−3.11


rc_T23468_at
884
T23468
CGI-119 protein
3.6
−4.67


AA195678_at
117
AA195678
actin binding protein; macrophin (microfilament
3.6
−3.48





and actin filament cross-linker protein)


AB002335_at
460
AB002335
KIAA0337 gene product
3.6
−4.21


rc_AA598982_s_at
429
AA598982
KIAA1114 protein trophinin
3.6
−4.58


J03507_at
621
J03507
complement component 7
3.6
−6.21


J04130_s_at
625
J04130
small inducible cytokine A4 (homologous to
3.5
−4.76





mouse Mip-1b)


AA495865_at
421
AA495865
ESTs
3.5
−3.65


HG3543-HT3739_at

HG3543-
insulin-like growth factor 2 (somatomedin A)
3.5
−4.69




HT3739


rc_AA599662_s_at
439
AA599662
KIAA0534 protein
3.5
−4.32


rc_AA486072_i_at
410
AA486072
small inducible cytokine A5 (RANTES)
3.5
−3.88


rc_Z39983_s_at
1112
Z39983
KIAA0561 protein
3.5
−5.56


rc_F02333_at
523
F02333
hypothetical protein FLJ20093
3.5
−2.23


rc_AA151210_at
89
AA151210
ESTs
3.5
−4.20


rc_N92239_at
793
N92239
Wnt inhibitory factor-1
3.5
−3.06


rc_AA173223_at
108
AA173223
ESTs
3.5
−5.22


rc_T86148_s_at
919
T86148
pituitary tumor-transforming 1 interacting protein
3.5
−2.15


AA214688_at
129
AA214688
eukaryotic translation initiation factor 4B
3.5
−3.13


rc_AA216589_at
131
AA216589
ESTs
3.5
−4.40


rc_AA446661_at
347
AA446661
hypothetical protein FLJ10970
3.4
−3.69


AA082546_at
54
AA082546
ESTs
3.4
−4.12


rc_W46395_at
1009
W46395
chromobox homolog 6
3.4
−2.41


rc_AA401433_at
257
AA401433
ESTs
3.4
−3.17


D62965_at
502
D62965
ESTs
3.4
−2.07


rc_AA057829_s_at
48
AA057829
growth arrest-specific 6
3.4
−2.00


rc_AA009755_at
6
AA009755
ESTs
3.3
−4.77


AA247204_at
163
AA247204
DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide
3.3
−2.85





16


D13628_at
476
D13628
angiopoietin 1
3.3
−4.86


rc_N59866_at
761
N59866
ESTs
3.3
−4.39


rc_AA406371_at
273
AA406371
ESTs
3.3
−4.98


rc_N67876_s_at
773
N67876
insulin-like growth factor 1 (somatomedin C)
3.3
−3.06


M84526_at
703
M84526
D component of complement (adipsin)
3.3
−3.06


rc_AA234095_at
144
AA234095
hypothetical protein FLJ20701
3.3
−3.78


rc_D60074_s_at
498
D60074
cadherin 10 (T2-cadherin)
3.3
−5.05


rc_T49602_s_at
896
T49602
ESTs
3.3
−3.36


rc_n22006_s_at
718
N22006
ESTs
3.3
−3.88


rc_F04112_f_at
530
F04112
ESTs
3.3
−3.26


rc_T64223_s_at
907
T64223
carboxypeptidase A3 (mast cell)
3.3
−2.97


U23946_at
955
U23946
RNA binding motif protein 5
3.2
−3.48


rc_AA358038_at
238
AA358038
SH3-binding domain glutamic add-rich protein
3.2
−3.21





like


rc_AA019433_at
12
AA019433
ESTs
3.2
−3.88


X03689_s_at
1044
X03689
eukaryotic translation elongation factor 1 alpha 1
3.2
−1.91


rc_H17550_at
559
H17550
ESTs
3.2
−2.90


rc_AA047880_at
38
AA047880
prothymosin, alpha (gene sequence 28)
3.2
−5.88


rc_AA084138_at
55
AA084138
ESTs
3.2
−7.93


rc_AA599365_at
434
AA599365
decorin
3.2
−4.42


rc_N91971_f_at
791
N91971
retinol-binding protein 1, cellular
3.2
−4.13


rc_T62873_at
904
T62873
ESTs
3.2
−2.12


rc_N49899_at
746
N49899
ESTs
3.2
−3.73


AA298981_at
226
AA298981
fibulin 5
3.2
−6.06


rc_AA479286_at
403
AA479286
ESTs
3.2
−3.54


J04111_at
624
J04111
v-jun avian sarcoma virus 17 oncogene homolog
3.2
−5.47


rc_AA465491_at
391
AA465491
Mad4 homolog
3.2
−2.75


W28548_at
997
W28548
ESTs
3.2
−3.59


AA308998_at
227
AA308998
endothelial differentiation-related factor 1
3.2
−2.89


rc_AA488432_at
412
AA488432
phosphoserine phosphatase
3.2
−3.48


rc_AA598991_at
430
AA598991
amyloid beta (A4) precursor protein-binding,
3.1
−4.51





family A, member 2 (X11-like)


AA463311_at
384
AA463311
hypothetical protein similar to mouse Fbw5
3.1
−2.57


rc_AA147224_at
85
AA147224
ESTs
3.1
−4.41


rc_AA609504_at
444
AA609504
fibronectin leucine rich transmembrane protein 2
3.1
−3.81


U20734_s_at
952
U20734
jun B proto-oncogene
3.1
−3.37


U06863_at
941
U06863
follistatin-like 1
3.1
−2.48


W51743_at
1011
W51743
ESTs
3.1
−2.95


rc_AA465093_at
389
AA465093
TIA1 cytotoxic granule-associated RNA-binding
3.1
−5.34





protein


rc_AA219100_at
132
AA219100
DKFZP586P2421 protein
3.1
−4.09


rc_R42424_at
832
R42424
ESTs
3.1
−3.82


rc_W73038_at
1026
W73038
ESTs
3.1
−2.23


AA091278_at
60
AA091278
hypothetical protein FLJ10793
3.1
−2.75


rc_AA620289_at
451
AA620289
PRO0518 protein
3.1
−2.55


rc_AA149579_at
87
AA149579
prostate cancer associated protein 1
3.1
−2.66


M21121_at
668
M21121
small inducible cytokine A5 (RANTES)
3.1
−4.97


rc_AA427890_at
312
AA427890
ESTs
3.1
−4.32


M34516_r_at
684
M34516
immunoglobulin lambda-like polypeptide 1
3.1
−3.47


rc_AA233347_at
140
AA233347
zinc finger protein 216
3.1
−2.43


rc_W74533_at
1029
W74533
latrophilin
3.1
−3.51


rc_AA029597_at
19
AA029597
bone morphogenetic protein 7 (osteogenic
3.1
−3.80





protein 1)


rc_N91887_s_at
790
N91887
thymosin, beta, identified in neuroblastoma cells
3.1
−4.47


rc_AA205724_at
123
AA205724
ESTs
3.0
−6.70


U30521_at
960
U30521
P311 protein
3.0
−6.06


X07109_at
1052
X07109
protein kinase C, beta 1
3.0
−4.90


D82346_at
511
D82346
potassium voltage-gated channel, KQT-like
3.0
−3.49





subfamily, member 2


rc_AA478962_at
400
AA478962
ESTs
3.0
−3.35


rc_AA151428_s_at
90
AA151428
matrix metalloproteinase 23A, matrix
3.0
−2.78





metalloproteinase 23B


rc_AA130349_at
73
AA130349
ESTs
3.0
−2.01


M18737_rna1_at
661
M18737
granzyme A (granzyme 1, cytotoxic T-
3.0
−5.90





lymphocyte-associated serine esterase 3)


rc_N91461_at
789
N91461
ESTs
3.0
−3.43


rc_AA045481_at
30
AA045481
ESTs
3.0
−3.70


U91903_at
989
U91903
frizzled-related protein
3.0
−4.73


U19495_s_at
950
U19495
stromal cell-derived factor 1
3.0
−4.38


M33493_s_at
680
M33493
tryptase, alpha, tryptase, beta (tryptase II)
3.0
−3.12


Y12711_at
1103
Y12711
progesterone binding protein
3.0
−2.33


rc_N58172_at
757
N58172
ESTs
3.0
−2.53


M12529_at
655
M12529
apolipoprotein E
3.0
−1.92


rc_AA412505_at
288
AA412505
ESTs
3.0
−3.35


U45955_at
967
U45955
glycoprotein M6B
3.0
−4.09


rc_H56673_at
581
H56673
ESTs
3.0
−4.25


L33799_at
645
L33799
procollagen C-endopeptidase enhancer
3.0
−4.72


rc_Z40186_at
1114
Z40186
ESTs
3.0
−2.22


AA094800_at
64
AA094800
eukaryotic translation initiation factor 3, subunit 7
2.9
−2.56





(zeta, 66/67 kD)


D21063_at
480
D21063
minichromosome maintenance deficient (S.
2.9
−5.27





cerevisiae) 2 (mitotin)


rc_AA412049_at
284
AA412049
ESTs
2.9
−2.63


rc_AA599661_at
438
AA599661
ESTs
2.9
−8.62


L02870_s_at
633
L02870
collagen, type VII, alpha 1 (epidermolysis
2.9
−4.69





bullosa, dystrophic, dominant and recessive)


rc_AA232266_s_at
138
AA232266
ESTs
2.9
−3.22


L02321_at
631
L02321
glutathione S-transferase M5
2.9
−3.33


rc_AA428325_at
315
AA428325
SEC14 (S. cerevisiae)-like 2
2.9
−3.52


D82534_at
512
D82534
f-box and leucine-rich repeat protein 5
2.9
−2.20


rc_T32113_at
889
T32113
KIAA0657 protein
2.9
−2.47


rc_R10896_at
808
R10896
cytochrome c oxidase subunit VIIa polypeptide 2
2.9
−1.99





like


rc_AA019034_i_at
11
AA019034
ESTs
2.9
−4.40


D28423_at
485
D28423
ESTs
2.9
−2.31


rc_AA609943_at
449
AA609943
ESTs
2.9
−3.86


W69302_at
1023
W69302
ESTs
2.9
−2.68


rc_H01824_f_at
544
H01824
GATA-binding protein 2
2.9
−3.82


rc_T67105_s_at
910
T67105
ESTs
2.9
−5.49


rc_AA426372_s_at
307
AA426372
H1 histone family, member X
2.9
−2.53


rc_T98288_f_at
933
T98288
ESTs
2.9
−2.66


rc_N63047_at
762
N63047
ESTs
2.9
−5.25


U57316_at
974
U57316
GCN5 (general control of amino-acid synthesis,
2.9
−3.59





yeast, homolog)-like 2


rc_AA219304_s_at
133
AA219304
alpha-2-macroglobulin
2.9
−1.76
















TABLE 4







Normal vs. BPH W/Symptoms Table (Down-regulated)













SEQ ID


Fold-



Affymetrix element
NO:
GenBank ID
GenBank Name
change
t















rc_T40895_at
892
T40895
protein tyrosine phosphatase type IVA, member
16.5
5.19





1


rc_N80129_i_at
785
N80129
metallothionein 1L
12.6
3.54


rc_AA460914_at
380
AA460914
ESTs
7.4
4.58


rc_AA234996_s_at
147
AA234996
cytochrome C oxidase subunit VIa polypeptide 2
7.2
4.10


X66141_at
1078
X66141
myosin, light polypeptide 2, regulatory, cardiac,
6.6
3.80





slow


AA234634_f_at
145
AA234634
CCAAT/enhancer binding protein (C/EBP), delta
6.2
4.35


rc_AA419011_at
296
AA419011
prostate androgen-regulated transcript 1
6.1
3.87


rc_N94303_at
797
N94303
ESTs
5.8
5.96


M20543_at
666
M20543
actin, alpha 1, skeletal muscle
5.5
3.20


rc_AA085943_s_at
58
AA085943
troponin T1, skeletal, slow
5.5
3.02


X06825_at
1050
X06825
tropomyosin 2 (beta)
5.2
3.35


AB000584_at
459
AB000584
prostate differentiation factor
5.1
3.80


M19309_s_at
665
M19309
troponin T1, skeletal, slow
5.0
3.41


rc_AA040433_at
24
AA040433
DKFZP586N2124 protein
5.0
2.62


rc_N32748_at
736
N32748
ESTs
5.0
3.36


rc_AA227926_at
135
AA227926
ESTs
4.8
5.39


rc_AA457566_at
375
AA457566
ESTs
4.7
4.22


rc_AA026641_s_at
16
AA026641
secretory leukocyte protease inhibitor
4.6
2.09





(antileukoproteinase)


rc_AA053424_at
40
AA053424
serine/threonine protein kinase MASK
4.5
4.16


V00594_at
992
V00594
metallothionein 2A
4.5
3.71


rc_R16983_at
811
R16983
ESTs
4.5
3.23


U75272_s_at
984
U75272
progastricsin (pepsinogen C)
4.4
4.57


rc_T94447_s_at
928
T94447
cortic al thymocyte receptor (X. laevis CTX) like
4.4
3.50


U08021_at
942
U08021
nicotinamide N-methyltransferase
4.4
2.41


J03910_rna1_at
622
J03910
metallothionein 1G
4.3
2.79


rc_AA236545_at
156
AA236545
ESTs
4.2
2.41


rc_AA211443_at
127
AA211443
ESTs
4.2
4.49


rc_AA398908_at
251
AA398908
ESTs
4.2
2.64


X57129_at
1067
X57129
H1 histone family, member 2
4.2
3.88


M21665_s_at
670
M21665
myosin, heavy polypeptide 7, cardiac muscle,
4.1
3.61





beta


X65614_at
1076
X65614
S100 calcium-binding protein P
4.1
4.03


rc_AA197112_r_at
119
AA197112
putative nuclear protein
4.1
3.07


M99487_at
716
M99487
folate hydrolase (prostate-specific membrane
4.0
2.65





antigen) 1


X04201_at
1045
X04201
neurotrophic tyrosine kinase, receptor, type 1
3.9
2.87


X05451_s_at
1046
X05451
ESTs
3.9
3.26


rc_AA435720_i_at
328
AA435720
tubulin, alpha 2
3.9
2.20


rc_N92502_s_at
794
N92502
ESTs
3.8
3.11


L77701_at
651
L77701
COX17 (yeast) homolog, cytochrome c oxidase
3.8
3.97





assembly protein


HG2157-HT2227_at

HG2157-
ESTs
3.8
4.08




HT2227


X76717_at
1087
X76717
metallothionein 1L
3.8
5.82


HG1067-HT1067_r_at

HG1067-
ESTs
3.7
3.02




HT1067


rc_AA599331_at
433
AA599331
CGI-119 protein, uncharacterized bone marrow
3.6
4.90





protein BM039


M20642_s_at
667
M20642
ESTs
3.6
3.48


rc_AA055163_at
44
AA055163
calsequestrin 2, cardiac muscle
3.6
3.66


rc_AA127946_at
72
AA127946
DKFZP586B2022 protein
3.6
4.40


rc_AA022886_at
14
AA022886
retinal degeneration B beta
3.6
3.51


rc_AA342337_at
231
AA342337
ESTs
3.5
2.57


X02544_at
1042
X02544
orosomucoid 1
3.5
1.92


rc_T73433_s_at
912
T73433
angiotensinogen
3.5
3.10


M21494_at
669
M21494
creatine kinase, muscle
3.4
2.46


rc_AA488072_s_at
411
AA488072
cardiac ankyrin repeat protein
3.4
2.78


rc_AA293187_s_at
223
AA293187
B-cell CLL/lymphoma 3
3.4
1.62


rc_AA599522_r_at
437
AA599522
squamous cell carcinoma antigen recognised by
3.4
3.03





T cells


rc_AA405488_at
268
AA405488
ESTs
3.4
2.57


rc_AA461453_at
382
AA461453
calcium binding protein Cab45 precursor,
3.4
3.10


rc_AA609006_at
440
AA609006
ESTs
3.4
2.30


rc_N24761_at
725
N24761
TU12B1-TY protein
3.4
3.89


rc_AA432162_at
324
AA432162
DKFZP586B2022 protein
3.4
2.78


X06256_at
1047
X06256
integrin, alpha 5 (fibronectin receptor, alpha
3.4
4.51





polypeptide)


rc_AA045825_at
33
AA045825
ESTs
3.3
3.90


rc_AA478778_at
399
AA478778
ESTs
3.3
4.37


rc_N80129_f_at
785
N80129
metallothionein 1L
3.2
3.60


rc_AA182030_at
110
AA182030
pyruvate dehydrogenase kinase, isoenzyme 4
3.2
3.72


rc_AA102489_at
67
AA102489
hypothetical protein FLJ10337
3.2
2.20


rc_R46074_at
840
R46074
transforming, acidic coiled-coil containing protein
3.2
3.38





2


rc_AA599522_f_at
437
AA599522
squamous cell carcinoma antigen recognised by
3.2
2.36





T cells


rc_AA165313_at
104
AA165313
ESTs
3.2
2.76


rc_AA429636_at
319
AA429636
hexokinase 2
3.2
3.12


rc_R71792_s_at
855
R71792
thrombospondin 1
3.1
2.31


U05861_at
940
U05861
aldo-keto reductase family 1, member C1
3.1
2.62





(dihydrodiol dehydrogenase 1; 20-alpha (3-





alpha)-hydroxysteroid dehydrogenase), aldo-keto





reductase family 1, member C2 (dihydrodiol





dehydrogenase 2; bile acid binding protein; 3-





alpha hydroxysteroid dehydrogenase, type III)


rc_AA410311_at
275
AA410311
ESTs
3.1
3.52


rc_AA505136_at
426
AA505136
ESTs
3.1
3.00


rc_T68873_f_at
911
T68873
metallothionein 1L
3.0
3.18


X00371_ma1_at
1041
X00371
myoglobin
3.0
2.18


rc_AA099820_at
65
AA099820
ESTs
3.0
3.08


rc_T90190_s_at
925
T90190
H1 histone family, member 2
3.0
3.48


rc_AA227936_f_at
136
AA227936
parathymosin
3.0
1.76


X90568_at
1092
X90568
titin
3.0
2.83


rc_AA004699_at
1
AA004699
orphan G-protein coupled receptor
3.0
2.23


rc_F03969_at
528
F03969
ESTs
2.9
2.53


X93036_at
1093
X93036
FXYD domain-containing ion transport regulator
2.9
2.91





3


rc_R91484_at
863
R91484
ESTs
2.9
6.43


rc_AA025370_at
15
AA025370
K1AA0872 protein
2.9
2.87


X51441_s_at
1063
X51441
serum amyloid A1
2.9
1.78


X64177_f_at
1075
X64177
metallothionein 1H
2.9
3.36


rc_AA255480_at
173
AA255480
ECSIT
2.9
2.38


rc_AA476944_at
394
AA476944
ESTs
2.8
4.26


U78294_at
985
U78294
arachidonate 15-lipoxygenase, second type
2.8
1.82


rc_AA045487_at
31
AA045487
ESTs
2.8
2.75


rc_N74291_at
779
N74291
ESTs
2.8
1.88


rc_N91973_at
792
N91973
hypothetical protein,three prime repair
2.8
1.97





exonuclease 1


D81655_at
510
D81655
ESTs
2.8
1.89


U53225_at
971
U53225
sorting nexin 1
2.8
3.16


rc_H77597_f_at
594
H77597
metallothionein 1H
2.8
2.98


K02215_at
628
K02215
angiotensinogen
2.8
3.05


rc_AA464728_s_at
388
AA464728
ESTs
2.7
3.80


rc_W49708_at
1010
W49708
ESTs
2.7
3.52


rc_AA453435_at
364
AA453435
ESTs
2.7
4.78


rc_D11824_at
474
D11824
ESTs
2.7
3.70


rc_T56281_f_at
902
T56281
RNA helicase-related protein
2.7
2.62


rc_AA182882_at
111
AA182882
titin-cap (telethonin)
2.7
1.85


rc_AA447522_at
349
AA447522
ESTs
2.7
3.27


rc_N26904_at
731
N26904
FK506 binding protein precursor
2.7
3.21


rc_AA131919_at
75
AA131919
putative type II membrane protein
2.7
4.15


rc_R89840_at
862
R89840
ESTs
2.7
2.23


rc_W31470_at
998
W31470
thyroid hormone receptor-associated protein, 95-
2.7
2.85





kD subunit


rc_W92207_at
1036
W92207
ESTs
2.7
4.07


U96094_at
990
U96094
sarcolipin
2.7
2.23


rc_W70131_at
1024
W70131
ESTs
2.7
3.64


rc_AA435720_f_at
328
AA435720
tubulin, alpha 2
2.7
1.98


rc_AA284879_at
212
AA284879
ESTs
2.7
1.74


rc_H22453_at
564
H22453
ESTs
2.7
4.20


D14826_s_at
478
D14826
cAMP responsive element modulator
2.6
4.13


rc_N93798_at
796
N93798
protein tyrosine phosphatase type IVA, member
2.6
3.12





3


U41804_at
965
U41804
putative T1/ST2 receptor binding protein
2.6
4.37


rc_W20486_f_at
995
W20486
chromosome 21 open reading frame 56
2.6
2.74


rc_AA055768_at
45
AA055768
CGI-119 protein
2.6
2.13


rc_AA447977_s_at
352
AA447977
ESTs
2.6
3.22


AA380393_at
243
AA380393
SEC7 homolog
2.6
2.29


rc_N29568_at
732
N29568
thyroid hormone receptor-associated protein,
2.6
2.46





150 kDa subunit


rc_AA426374_f_at
308
AA426374
tubulin, alpha 2
2.6
3.20


rc_H94471_at
604
H94471
occludin
2.6
2.19


rc_AA252219_at
169
AA252219
ESTs
2.6
3.83


rc_AA402000_at
259
AA402000
ESTs
2.6
2.29


rc_Z38744_at
1108
Z38744
putative gene product
2.6
4.18


AA045870_at
34
AA045870
ESTs
2.6
2.26


rc_R38678_at
823
R38678
ESTs
2.6
4.16


R39467_f_at
826
R39467
NEU1 protein
2.6
2.79


AA455001_s_at
368
AA455001
CGI-43 protein
2.6
5.34


rc_AA292328_at
221
AA292328
activating transcription factor 5
2.6
2.88


X57348_s_at
1068
X57348
stratifin
2.6
2.48


rc_T95005_s_at
929
T95005
ESTs
2.5
3.30


AA410355_at
276
AA410355
ribosomal protein S6 kinase, 70 kD, polypeptide
2.5
2.31


AA036900_at
21
AA036900
ESTs
2.5
2.45


rc_F02204_at
521
F02204
BAI1-associated protein 2
2.5
2.26


U26173_s_at
958
U26173
nuclear factor, interleukin 3 regulated
2.5
3.91


rc_AA477767_at
396
AA477767
ESTs
2.5
3.17


rc_AA504805_s_at
424
AA504805
interferon stimulated gene (20 kD)
2.5
3.79


rc_R33627_i_at
818
R33627
ESTs
2.5
1.99


rc_T40995_f_at
893
T40995
alcohol dehydrogenase 3 (class I), gamma
2.5
2.15





polypeptide


rc_R00144_at
801
R00144
ESTs
2.5
2.69


U02020_at
936
U02020
pre-B-cell colony-enhancing factor
2.5
4.20


rc_AA287832_at
217
AA287832
ESTs
2.5
3.80


AA429539_f_at
318
AA429539
hypothetical protein
2.5
2.35


rc_H05084_at
547
H05084
GDP-mannose pyrophosphorylase B
2.5
2.23


rc_AA405616_at
271
AA405616
ESTs
2.5
3.33


AA455381_at
370
AA455381
aldehyde dehydrogenase 5 family, member A1
2.4
2.60





(succinate-semialdehyde dehydrogenase)


M13955_at
658
M13955
keratin 7
2.4
2.22


rc_AA180314_at
109
AA180314
ESTs
2.4
2.53


M37984_rna1_at
688
M37984
troponin C, slow
2.4
2.10


M61764_at
694
M61764
tubulin, gamma 1
2.4
3.48


rc_AA150920_at
88
AA150920
KIAA0539 gene product
2.4
4.11


X65965_s_at
1077
X65965
superoxide dismutase 2, mitochondrial
2.4
2.37


X93510_at
1094
X93510
LIM domain protein
2.4
2.39


rc_N48056_s_at
745
N48056
folate hydrolase (prostate-specific membrane
2.4
1.80





antigen) 1


rc_N26713_s_at
729
N26713
ESTs
2.4
3.87


rc_AA282247_at
204
AA282247
ESTs
2.4
3.17


rc_D80617_at
508
D80617
KIAA0596 protein
2.4
2.02


rc_F02245_at
522
F02245
monoamine oxidase A
2.4
2.79


rc_R58878_at
847
R58878
ESTs
2.4
2.80


rc_W45531_at
1007
W45531
ESTs
2.4
4.17


L25270_at
644
L25270
SMC (mouse) homolog, X chromosome
2.4
3.26


rc_W88568_at
1035
W88568
glycogenin 2
2.4
1.90


rc_AA070752_s_at
51
AA070752
insulin receptor substrate 1
2.4
2.87


U24169_at
956
U24169
JTV1 gene,hypothetical protein PRO0992
2.4
3.41


rc_T15423_s_at
878
T15423
2′,3′-cyclic nucleotide 3′ phosphodiesterase
2.4
1.71


X78706_at
1088
X78706
carnitine acetyltransferase
2.4
3.51


rc_T10695_i_at
876
T10695
enigma (LIM domain protein) 2.4
1.52


rc_AA430388_at
321
AA430388
HSPC160 protein
2.4
5.04


M68519_rna1_at
699
M68519
surfactant, pulmonary-associated protein A1
2.4
3.89


rc_AA421562_at
300
AA421562
anterior gradient 2 (Xenepus aevis) homolog
2.4
1.80


rc_T97243_at
931
T97243
prenyl protein protease RCE1
2.4
2.46


rc_T15409_f_at
877
T15409
ESTs
2.3
3.76


rc_T62918_at
905
T62918
ESTs
2.3
2.59


rc_R15108_at
810
R15108
ESTs
2.3
2.74


AA454908_s_at
366
AA454908
KIAA0144 gene product
2.3
2.77


rc_N64683_at
764
N64683
CGI-119 protein
2.3
2.27


rc_H99035_at
612
H99035
ESTs
2.3
4.34


Y08374_rna1_at
1100
Y08374
chitinase 3-like 1 (cartilage glycoprotein-39)
2.3
2.94


rc_AA236241_at
150
AA236241
ESTs
2.3
1.57


U52969_at
970
U52969
Purkinje cell protein 4
2.3
3.49


rc_R11526_f_at
809
R11526
parathymosin
2.3
1.71


rc_T15850_f_at
880
T15850
ESTs
2.3
2.42


HG2259-HT2348_s_at

HG2259-
tubulin, alpha 1 (testis specific), tubulin, alpha,
2.3
2.91




HT2348
ubiquitous


rc_H15143_s_at
554
H15143
ortholog of rat pippin
2.3
1.45


rc_AA101767_at
66
AA101767
ESTs
2.3
3.52


rc_AA193197_at
116
AA193197
sarcomeric muscle protein
2.3
1.98


U03688_at
938
U03688
cytochrome P450, subfamily I (dioxin-inducible),
2.3
2.97





polypeptide 1 (glaucoma 3, primary infantile)


rc_R37774_at
822
R37774
cytochrome P450 retinoid metabolizing protein
2.3
4.11


rc_H81413_f_at
597
H81413
high-mobility group (nonhistone chromosomal)
2.3
3.12





protein isoforms I and Y


X16354_at
1060
X16354
carcinoembryonic antigen-related cell adhesion
2.3
2.54





molecule 1 (biliary glycoprotein)


rc_AA457235_at
373
AA457235
ESTs
2.3
2.25


D13643_at
477
D13643
KIAA0018 gene product
2.3
1.78


rc_N30856_at
734
N30856
solute carrier family 19 (thiamine transporter),
2.3
3.45





member 2


M26311_s_at
673
M26311
S100 calcium-binding protein A9 (calgranulin B)
2.3
2.37


rc_Z40556_at
1116
Z40556
CGI-96 protein
2.3
2.39


rc_N79070_at
783
N79070
ESTs
2.3
1.43


Z69881_at
1122
Z69881
ATPase, Ca++ transporting, ubiquitous
2.3
3.87


rc_D60755_s_at
500
D60755
ESTs
2.3
2.30


rc_N94424_at
798
N94424
retinoic acid receptor responder (tazarotene
2.2
1.09





induced) 1

















TABLE 5







Up-regulated genes
Down-regulated genes










Cluster
Fragment Name
Cluster
Fragment Name





1
rc_AA256268_at
1
rc_AA227926_at


1
rc_AA188981_at
1
rc_AA398908_at


1
rc_AA173223_at
1
L77701_at


1
rc_AA216589_at
1
rc_AA599331_at


1
rc_AA234095_at
1
AA455001_s_at


1
rc_H17550_at
3
rc_AA022886_at


1
AA308998_at
3
rc_N24761_at


1
rc_AA488432_at
3
X06256_at


1
rc_AA427890_at
4
HG1067-HT1067_r_at


1
rc_N91887_s_at
4
rc_AA127946_at


1
rc_AA045481_at
4
rc_AA405488_at


3
rc_T23622_at
5
AA234634_f_at


3
rc_T23490_s_at
5
X65614_at


3
rc_AA620289_at
5
rc_T73433_s_at


4
rc_H05704_r_at
5
rc_R91484_at


4
rc_AA436616_at
5
rc_N93798_at


4
rc_AA456147_at
6
rc_N94303_at


4
rc_f09748_s_at, AA495865_at
6
AB000584_at


4
rc_AA598982_s_at
6
rc_AA410311_at


4
HG3543-HT3739 at
6
rc_F02245_at


4
rc_AA609504_at
7
rc_T40895_at


5
rc_AA028092_s_at
7
rc_N80129_i_at, X76717_at





rc_N80129_f_at, rc_T68873_f_at


5
U62015_at
7
rc_N32748_at


5
rc_F13763_at
7
V00594_at


5
rc_AA205724_at
7
J03910_rnal_at


5
U30521_at
7
X57129_at, rc_T90190_s_at


6
X52541_at
7
rc_AA182030_at


6
rc_AA281345_f_at, M62831_at
7
rc_AA505136_at


7
rc_n22006_s_at
7
X64177_f_at, rc_H77597_f_at


7
rc_R42424_at
7
rc_AA101767_at
















TABLE 6







BPH vs. Normal and Cancer









P-Values




















Normal
Normal
Normal
BPHWS
BPHWS
BPHNoS


Affymetrix
SEQ ID


vs.
vs.
vs.
vs.
vs.
vs.


Fragment Name
NO:
GenBank ID
GenBank Name
BPHWS
BPHNoS
Cancer
BPHNoS
Cancer
Cancer



















AA092215_at
61
AA092215
potassium channel modulatory factor
0.1086431
0.887604969
0.000105867
0.141381127
0.031099165
0.000775399


AA122242_at
70
AA122242
mannose-6-phosphatereceptor (cation
7.49E−05
0.560180168
0.87992066
0.006231736
0.000301953
0.664273011





dependant)


AA122302_at
71
AA122302

0.430127474
0.003373118
0.068806262
0.000514723
0.328161735
1.48715E−05


AA155958_at
94
AA155958
S164 protein
0.096247016
0.007959573
0.170003368
8.36688E−05
0.782399153
0.000223021


AA236286_at
151
AA236286
fetal Alzheimer antigen
0.052450894
0.034104742
0.076032207
0.000262856
0.875443134
0.000444882


AA248802_at
165
AA248802
DKFZP564A122 protein
0.000230259
0.38257085
0.842458286
0.026030678
0.000947368
0.500601376


AA293544_at
225
AA293544
D component of complement (adipsin)
7.02821E−05
0.203858328
0.178154822
5.9415E−06
0.012632481
0.019226603


AA376488_at
242
AA376468

0.405364589
0.000353844
0.537460601
0.006147013
0.169320077
7.97148E−05


AA410925_at
278
AA410925
transducin-like enhancer of split 1,
0.870505598
1.09859E−05
0.106359333
4.33855E−05
0.168431987
0.003967521





homolog of Drosophila E(sp1)


AA461618_s_at
383
AA461618
0.001614433
0.497688178
0.000768417
0.001055794
6.29856E−10
0.031759146


C15965_at
468
C15965

0.000459149
0.350724893
0.919693498
0.000138025
0.000627643
0.416397432


D10537_s_at
472
D10537
myelin protein zero (Charcot-Marie-Tooth
4.11477E−05
0.923679005
4.72641E−05
0.000899706
0.975645863
0.00098994





neuropathy 1B)


D25303_at
482
D25303
integrin, alpha 9
0.00061935
0.196221991
0.000846365
0.108182462
0.935105808
0.124782864


D26598_at
483
D26598
proteasome (prosome, macropain) subunit,
0.000121781
0.02105211
8.45942E−05
0.326778603
0.933101073
0.291769938





beta type, 3


D31887_at
489
D31887
K1AA0062 protein
0.000123265
0.125782983
0.000676946
0.084742928
0.675822922
0.174766454


D50532_at
492
D50532
macrophage lectin 2 (calcium dependent)
0.013806312
0.034992941
0.07897755
0.981647465
6.26998E−05
0.000487842


D50550_at
493
D50550
lethal giant larvae (Drosophila) homolog 1
3.10455E−05
0.029363545
4.06139E−05
0.169772872
0.953324091
0.186302331


D64154_at
503
D64154
cell membrane glycoprotein, 110000M(r)
1.68633E−05
0.000696104
5.008732-05
0.747380424
0.814285971
0.90759386





(surface antigen)


D84294_at
514
D84294
tetratricopeptide repeat domain 3
8.04076E−06
0.163620727
0.000752223
0.017501269
0.299205599
0.142785528


D86976_at
515
D86976
minor histocompatibility antigen HA-1
3.35538E−06
0.219311742
4.36833E−07
0.007209475
0.701246025
0.002498824


D87258_at
516
D87258
protease, serine, 11 (IGF binding)
9.00737E−05
0.762310231
0.004565624
0.000386998
0.305696637
0.008038934


D87292_at
517
D87292
thiosulfate sulfurtransferase (rhodanese)
0.004418719
0.000188241
0.000878154
0.222741306
0.648642702
0.412420863


D87465_at
518
D87465
KIAA0275 gene product
7.37644E−05
0.826724125
0.000140053
0.000450807
0.882546967
0.000727958


H19969_at
562
H19969

0.005160656
7.47697E−07
6.71287E−07
0.01521142
0.039287107
0.535558762


H61361_s_at
587
H61361
immunoglobulin superfamily containing
4.92249E−05
0.834280925
5.95931E−05
0.001490555
0.966053313
0.001694157





leucine-rich repeat


J00277_at
618
J00277
v-Ha-ras Harvey rat sarcoma viral oncogene
0.035655118
0.055426457
0.009927846
0.000332747
0.650555821
6.72893E−05





homolog


J04076_at
623
J04076
early growth response 2 (Krox-20 (Drosophila)
0.034912914
0.473833846
2.46869E−11
0.285997211
1.48067E−05
1.13903E−06





homolog)


J04605_at
627
J04605
peptidase D
0.000200727
0.006030981
0.000362209
0.648903631
0.885410388
0.742239283


K03204_f_at
630
K03204
proline-rich protein BstNI subfamily 1
0.283795673
0.000798814
0.913648897
0.019814734
0.26284107
0.000926711


L02326_f_at
632
L02326

0.105345943
0.659037818
6.62426E−05
0.076492051
0.02455672
0.000181614


L05500_at
635
L05500
adenylate cyclase 1 (brain)
0.016699778
0.257619651
3.79921E−05
0.002077455
0.101519111
6.32745E−06


L06797_s_at
636
L06797
chemokine (C-X-C motif), receptor 4 (fusin)
0.443118956
0.447152817
1.30523E−06
0.926525008
0.000111977
0.000981046


L08246_at
637
L08246
myeloid cell leukemia sequence 1 (BCL2-related)
0.043208838
0.230033308
4.68128E−10
0.596833839
6.55684E−05
5.57731E−05


L13740_at
639
L13740
nuclear receptor subfamily 4, group A, member 1
0.791312753
0.872331125
8.60985E−05
0.70798804
7.00025E−05
0.001852799


L13852_at
640
L13852
ubiquitin-activating enzyme E1-like
0.000578096
0.646204921
0.003882395
0.000950816
0.599103668
0.004460291


L19437_at
641
L19437
transaldolase 1
0.008021968
0.22883538
0.001388037
0.000773689
0.604482478
0.000135454


L34587_at
646
L34587
transcription elongation factor B (SIII),
0.000178315
0.105125832
7.09176E−05
0.11839964
0.830767426
0.080296411





polypeptide 1 (15 kD, elongin C)


L44497_at
648
L44497
cyclic AMP phosphoprotein, 19 kD
0.000816364
0.012044336
0.000161685
0.709380948
0.686659704
0.467540879


L76200_at
650
L76200
guanylate kinase 1
0.000841699
0.002396122
0.000888336
0.889388751
0.988638065
0.879528075


M12959_s_at
656
M12959
T cell receptor alpha locus
3.02601E−08
0.817611534
3.24058E−08
1.14437E−05
0.990909384
1.1981E−05


M13560_s_at
657
M13560
CD74 antigen (invariant polypeptide of major
0.01541788
0.255419127
4.82527E−06
0.001882075
0.041399052
9.73079E−07





histocompatibility complex, class II antigen-associated)


M14660_at
659
M14660

1.95092E−06
0.823404837
0.009910008
0.000180501
0.038673415
0.053432817


M16336_s_at
660
M16336
CD2 antigen (p50), sheep red blood cell receptor
0.000908965
0.444045616
0.000106508
0.042888317
0.596564762
0.01280799


M19154_at
663
M19154
transforming growth factor, beta 2
0.021033675
0.886661499
5.38416E−05
0.039706043
0.100571645
0.00047052


M19283_at
664
M19283
actin, gamma 1
0.009680549
0.975542421
1.35524E−05
0.029109597
0.094241798
0.000262549


M21121_s_at
668
M21121
small inducible cytokine A5 (RANTES)
0.00011935
0.82444906
0.028900951
0.000639223
0.114726075
0.042253328


M31776_s_at
677
M31776
natriuretic peptide precursor B
9.53305E−05
0.786764461
0.00132485
0.000453681
0.511730949
0.003376181


M33552_at
681
M33552
lymphocyte-specific protein 1
0.098325681
0.187562681
0.000373789
0.008253387
0.070738695
2.37353E−05


M37766_at
687
M37766
CD48 antigen (B-cell membrane protein)
0.006750544
0.671986725
0.000173892
0.007796504
0.321364096
0.000414775


M54927_at
689
M54927
proteolipid protein (Pelizaeus-Merzbacher
0.0008203
0.071504547
0.000610665
0.292633338
0.938762949
0.26282367





disease, spastic paraplegia 2, uncomplicated)


M59465_at
691
M59465
tumor necrosis factor, alpha-induced protein 3
0.905275899
0.300604716
2.40334E−05
0.370512119
3.79139E−05
6.51796E−06


M60459_at
693
M60459
erythropoietin receptor
5.33228E−07
0.001997812
2.00307E−06
0.229150396
0.804556624
0.324369463


M73077_at
701
M73077
glucocorticoid receptor DNA binding factor 1
4.33165E−05
0.026210722
7.3229E−05
0.205361352
0.906734945
0.244557908


M89796_rna1_at
705
M89796
membrane-spanning 4-domains, subfamily A, member 1
3.38097E−07
0.68414038
0.000659504
0.000116527
0.107834095
0.014565483


M94077_at
709
M94077
loricrin
7.86788E−05
0.167396165
8.55841E−06
0.050135902
0.633682729
0.017465235


M94547_at
710
M94547
myosin light chain 2a
0.000922884
0.001567598
0.000142192
0.778547965
0.641162082
0.898495047


M95678_at
712
M95678
phospholipase C, beta 2
2.65752E−06
0.741444839
0.00021566
0.000330645
0.344847831
0.005753116


M96995_5_at
713
M96995
growth factor receptor-bound protein 2
0.000451432
0.370687613
0.000417356
0.039514013
0.984237779
0.037882757


M98447_rna1_at
714
M98447
transglutaminase 1 (K polypeptide epidermal
0.101078475
0.000501168
0.49866517
0.047778543
0.027993512
9.36193E−05





type I, protein-glutamine-gamma-glutamyltransferase)


N24990_a_at
728
N24990

0.000594989
0.692375474
0.833157714
0.001206749
0.00054518
0.837698657


R08720_at
805
R08720
hypothetical protein FLJ22609
0.384088189
0.004709624
0.405658837
0.000582614
0.970613897
0.000656156


R33301_at
817
R33301

0.263328276
0.008898636
0.324726425
0.000573184
0.899017203
0.000860093


R39394_at
825
R39394
E1B-55 kDa-associated protein 5
0.000120098
0.168965093
0.159597216
5.8721E−06
0.020650662
0.012378795


rc_AA004901_at
2
AA004901

0.00013
0.114226367
0.898931127
2.58485E−06
0.000448774
0.104547963


rc_AA005382_s_at
3
AA005382
granzyme K (serine protease, granzyme 3; tryptase II)
4.06793E−05
0.956799991
0.000100487
0.000772831
0.838991074
0.001451838


rc_AA009615_at
5
AA009615

7.69548E−05
0.013016412
0.000583037
0.366115762
0.625611179
0.634185041


rc_AA010358_at
7
AA010358

1.36211E−06
0.550401822
0.139035486
0.000570081
0.001477269
0.511053692


rc_AA017547_r_at
9
AA017547
hypothetical protein FLJ12387 similar to kinesin light chain
0.989540408
0.214430361
0.000274727
0.228713943
0.000584071
2.44522E−05


rc_AA018414_at
10
AA018414

0.556560157
0.000998026
0.519992597
0.000261037
0.958086097
0.000217926


rc_AA022615_at
13
AA022615
RNA binding motif protein 9
0.000158793
0.509341291
0.263342589
0.000159018
0.011670476
0.117665916


rc_AA037828_at
22
AA037828

0.000583981
0.645542969
0.84290982
0.000955558
0.002108779
0.543978545


rc_AA043196_at
26
AA043196
SMC (mouse) homolog, X chromosome
0.008527895
0.000983583
0.000257323
0.328438436
0.331116816
0.90061816


rc_AA053267_at
39
AA053267
K1AA1023 protein
0.000119181
0.288536772
0.388296579
2.42934E−05
0.004627114
0.082295734


rc_AA053883_at
41
AA053883

4.95718E−05
0.962839667
0.16054889
0.000624096
0.01179586
0.225390364


rc_AA054222_at
42
AA054222

0.39176403
0.002571399
0.102566251
0.000307234
0.461555799
2.09152E−05


rc_AA055081_at
43
AA055081

6.36828E−05
0.206434411
0.797911434
5.59851E−06
5.42681E−05
0.316914958


rc_AA065173_at
49
AA065173
chromosome 5 open reading frame 4
2.526782-07
0.570857861
0.058275966
0.000180212
0.001970189
0.302526217


rc_AA069913_at
50
AA069913

0.653765843
0.52776555
5.65709E−06
0.815416554
0.000104293
0.00152505


rc_AA071558_at
52
AA071558

0.168309619
0.418677904
0.000189452
0.054446269
0.025471654
0.000103274


rc_AA082041_at
53
AA082041
likely homolog of rat kinase 0-interacting
0.000143369
0.247732655
0.871515758
0.040056839
0.000552895
0.3290855





substance of 220 kDa; KIAA1250 protein


rc_AA084324_at
56
AA084324

0.000226203
0.056433291
0.000687497
0.216607531
0.780835192
0.321404997


rc_AA085608_at
57
AA085608
KIAA1041 protein
0.029391584
0.03435634
0.041546789
0.000120442
0.894217078
0.000192545


rc_AA114858_at
68
AA114858
tyrosine 3-monooxygenase/tryptophan 5-monooxygenase
0.000210292
0.155417252
0.994165585
8.636522-06
0.000449478
0.170373425





activation protein, eta polypeptide


rc_AA132239_at
76
AA132239

0.012168107
5.56988E−05
4.55236E−05
0.074087524
0.136307788
0.631558319


rc_AA132453_at
77
AA132453

0.000489304
0.141814616
8.74406E−05
0.136343527
0.678807616
0.063921338


rc_AA138864_at
81
AA136864
zinc finger protein homologous to Zfp-36 in mouse
0.000224205
0.630168118
4.90412-05
0.009114985
0.72551107
0.003549498


rc_AA143190_s_at
83
AA143190
CGI-147 protein
5.31694E−05
0.028242427
0.000127165
0.209594394
0.842566905
0.279924929


rc_AA143467_at
84
AA143467
hypothetical protein FLJ20343
1.62361E−06
0.259338862
1.37865E−06
0.003657312
0.975267724
0.003351742


rc_AA149051_at
86
AA149051

4.08493E−05
0.490333235
0.026825837
4.57567E−05
0.07318676
0.012248149


rc_AA152408_at
93
AA152408
K1AA0433 protein
2.97974E−05
0.362537361
0.455914763
1.36986E−05
0.001140199
0.13486533


rc_AA156064_at
95
AA156064

0.275270351
0.000333624
0.875633108
0.011111677
0.23661308
0.000347347


rc_AA158132_at
98
AA158132
nudix (nucleoside diphosphate linked moiety X)-type motifs
0.004899515
0.643469716
4.65182E−07
0.057915819
0.034659352
0.000177571


rc_AA165116_at
101
AA165116

0.000334885
0.681603266
0.211571862
0.000813512
0.029042963
0.151679697


rc_AA165231_at
102
AA165231

0.002549485
0.173959444
0.254670513
0.000135147
8.0406E−05
0.719982481


rc_AA169837_at
105
AA169837
NADH dehydrogenase (ubiquinone) Fe—S
0.08971279
0.008766485
0.091371238
8.4903E−05
0.993409911
8.74977E−05





protein 6 (13 kD) (NADH-coenzyme Q reductase)


rc_AA172188_at
107
AA172188
protocadherin alpha 5
0.000667976
0.267150381
4.96881E−06
0.077589163
0.269599078
0.006273958


rc_AA189015_at
113
AA189015
aminolevulinate, delta-, synthase 2
0.083660421
0.006384313
1.64695E−08
0.237580015
0.000203416
0.037803249





(sideroblastic/hypochromic anemia)


rc_AA192553_at
115
AA192553
uncoupling protein 3 (mitochondrial, proton carrier)
0.10098208
0.00017981
0.933630822
0.02546947
0.102059527
0.000244309


rc_AA196549_at
118
AA196549

0.001049824
0.569766558
0.000482225
0.001065463
0.839463674
0.000559925


rc_AA205072_at
120
AA205072
KIAA0980 protein
0.000335755
0.586934845
0.684865398
0.000455367
0.002552925
0.389985886


rc_AA205460_at
122
AA205460

0.000108573
0.165439416
0.84259483
5.28568E−06
0.000494762
0.134180366


rc_AA205947_at
124
AA205947
HHGP protein
0.000271962
0.552878143
0.70583219
0.000318994
0.001963327
0.376568675


rc_AA207103_at
125
AA207103
amiloride-sensitive cation channel 2, neuronal
2.05331E−05
0.045239142
0.642629872
0.10526525
0.000317921
0.124103707


rc_AA211300_at
126
AA211300
KIAA0627 protein; Drosophila “multiple
0.004445798
0.287777463
0.006200387
0.000703498
0.918638362
0.000971608





asters” (Mast)-like homolog 2


rc_AA211835_s_at
128
AA211835
MHC class II transactivator
0.001672055
0.122505424
0.000371358
4.15083E−05
0.692673582
8.76636E−06


rc_AA215379_at
130
AA215379

7.98828E−05
0.366787682
0.194666913
3.33447E−05
0.012005727
0.051632715


rc_AA228020_at
137
AA228020
splicing factor (CC1.3)
0.00047128
0.328754864
0.940819016
0.000119264
0.001167483
0.317270472


rc_AA233545_at
141
AA233545
AD-003 protein
0.004492717
0.655215048
2.53288E−07
0.052976799
0.028149978
0.000113193


rc_AA233854_at
142
AA233854
S-phase kinase-associated protein 2 (p45)
3.799S4E−05
0.744241299
0.538817385
0.001845337
0.000884538
0.84309443


rc_AA233935_at
143
AA233935

0.000608235
0.578078963
0.30216801
0.00070772
0.023016587
0.163656536


rc_AA234631_at
146
AA234631
KIAA0788 protein
0.000575081
0.410892837
0.954178902
0.000257285
0.000897188
0.457935122


rc_AA236453_at
152
AA236453

0.036687413
0.061484767
0.023140149
0.000407818
0.863002571
0.000227528


rc_AA236477_at
155
AA236477
KIAA1559 protein
0.000207423
0.453577644
0.288868663
0.000140775
0.011962605
0.1090363


rc_AA236822_at
157
AA236822
KIAA1097 protein
0.008052957
0.439727961
0.000891185
0.003207259
0.52319673
0.000453056


rc_AA237011_at
158
AA237011
ATP-binding cassette, sub-family F (GCN20), member 1
0.000202964
0.000263744
1.87304E−06
0.678815593
0.318565402
0.645008985


rc_AA237034_at
159
AA237034
golgi SNAP receptor complex member 2
2.31824E−05
0.319635059
3.30639E−08
0.010320292
0.220104139
0.000272212


rc_AA243416_s_at
180
AA243416
hypothetical protein, expressed in osteoblast
0.033376619
4.72108E−05
0.469143753
0.032420785
0.182985166
0.000942701


rc_AA243698_at
161
AA243698
potassium channel modulatory factor
0.06151528
0.302492952
0.000486853
0.010884151
0.124764794
9.91149E−05


rc_AA243763_at
162
AA243763

0.050706904
0.01206437
0.11555761
5.40095E−05
0.71829242
0.000198301


rc_AA253361_at
172
AA253361

0.000564229
0.000110501
0.010769519
0.397832434
0.394174789
0.11120186


rc_AA255966_at
174
AA255966

0.000512371
0.381782918
0.000368364
0.040324542
0.933794518
0.03373143


rc_AA256486_at
177
AA256486
CGI-141 protein
0.053041853
0.519681482
0.000805238
0.025864118
0.179038095
0.000657368


rc_AA258585_at
180
AA258585
cadherin 19, type 2
8.77783E−08
0.008879695
3.84529E−06
0.0526509
0.488129443
0.183610463


rc_AA258595_f_at
181
AA258595
major histocompatibility complex, class II, DQ beta 1
0.056902737
0.411462581
1.12504E−05
0.017626477
0.018278908
8.86477E−06


rc_AA262107_at
183
AA262107

0.051109951
0.028221779
0.046925687
0.000190669
0.972441626
0.000168986


rc_AA262349_at
184
AA262349
hypothetical protein FLJ10628
0.023368538
0.075191389
0.000520191
0.000323092
0.25384504
4.28987E−06


rc_AA262477_at
185
AA262477
ribonuclease HI, large subunit
0.843423091
0.000293418
0.145801246
0.000917609
0.233064808
0.023283635


rc_AA262969_f_at
186
AA262969
px19-like protein
0.000697965
0.002321008
4.86461E−08
0.916139727
0.050019001
0.106622452


rc_AA278757_at
187
AA278757
KIAA1205 protein
0.000807747
0.701913497
0.00019298
0.001603897
0.719959281
0.000521168


rc_AA278887_at
189
AA278887

4.77289E−05
0.000505266
0.002921534
0.966491221
0.300838621
0.386804461


rc_AA279028_at
190
AA279028

0.269683575
0.000110029
0.896242284
0.00515459
0.355782598
0.000309622


rc_AA279774_at
194
AA279774

0.028330552
0.004250917
0.09766388
4.84994E−06
0.610845854
3.70943E−05


rc_AA279821_s_at
195
AA279821

0.01541818
0.057056528
0.036000999
0.00012115
0.75748484
0.000352962


rc_AA280297_at
196
AA280297

0.004904401
0.069649547
0.030554618
4.43102E−05
0.537205763
0.000396218


rc_AA280309_at
197
AA280309

0.027919295
0.048777883
0.042451847
0.000197325
0.872357649
0.000341621


rc_AA280617_at
198
AA280617

0.020747951
0.100016813
0.006218315
0.000457645
0.687853962
0.000114895


rc_AA282739_at
205
AA282739
Ser/Arg-related nuclear matrix protein (plenty of
0.006885251
0.224885918
0.001928329
0.000638964
0.705244944
0.000179491





prolines 101-like)


rc_AA283091_at
206
AA283091
KIAA1219 protein
0.000391955
0.950383286
0.000147487
0.003849943
0.812656175
0.001947884


rc_AA283772_at
207
AA283772
replication factor C (activator 1) 5 (36.5 kD)
0.472125644
0.004274231
0.126899001
0.00082772
0.443684418
5.94032E−05


rc_AA283774_at
208
AA283774

0.634799287
0.001085136
0.774459677
0.000408559
0.858121118
0.000730937


rc_AA283907_at
209
AA283907
DC12 protein
0.702306606
0.426110345
0.000364953
0.278959611
0.000181185
0.027738884


rc_AA284777_at
211
AA284777

0.00028958
0.613024306
0.843581256
0.0004624
0.001148934
0.515630593


rc_AA286862_at
214
AA286862
WD repeat domain 6
0.006465478
0.770956466
3.90332E−06
0.047019059
0.072475744
0.000368843


rc_AA287107_s_at
215
AA287107
zinc finger protein ZNF140-like protein
0.000557513
0.647966939
0.168481176
0.000931348
0.049075778
0.113081619


rc_AA287870_s_at
218
AA287870
lymphotoxin beta (TNF superfamily, member 3)
0.042868875
0.904123896
4.72641E−06
0.071763173
0.015492602
8.72095E−05


rc_AA291970_at
220
AA291970
lectomedin-2
0.133517759
0.00116479
0.062658963
1.25187E−05
0.731829127
3.02794E−06


rc_AA292533_at
222
AA292533
putative Rab5-interacting protein
8.63268E−05
0.143959708
1.94797E−06
0.062483153
0.429586131
0.010599279


rc_AA342918_at
232
AA342918
hypothetical protein FLJ22313
0.000298568
0.534260232
0.802167146
0.015864864
0.000243847
0.42047475


rc_AA347578_at
234
AA347578
tubulin, beta polypeptide
0.056066605
0.067322154
0.053415125
0.000815763
0.984081099
0.000765743


rc_AA348446_at
235
AA348446

0.00081514
0.498461887
0.002492252
0.000590962
0.75904915
0.001541743


rc_AA349417_at
236
AA349417

0.333508877
4.09468E−05
0.860387174
0.001709823
0.452900772
0.000147762


rc_AA370867_at
239
AA370867

0.000438073
0.000509149
0.076534621
0.678852203
0.097859647
0.062063558


rc_AA371520_at
240
AA371520

0.000956188
0.182406672
0.0004497
0.142299266
0.84509761
0.101288353


rc_AA398719_at
249
AA398719
homolog of rat nadrin
0.005171893
0.312848506
0.003453438
0.000980065
0.903295813
0.000667115


rc_AA399101_at
252
AA399101

0.020406213
0.066006562
0.014033951
0.000219359
0.896140692
0.00013891


rc_AA399542_f_at
254
AA399542

0.225479535
0.502403493
5.62157E−05
0.098347881
0.007549959
6.44137E−05


rc_AA400034_at
255
AA400034

0.250995551
0.01453561
0.033099094
0.00095651
0.35107658
3.77436E−05


rc_AA401297_s_at
256
AA401297
symplekin; Huntingtin interacting protein I
0.012585329
0.166831042
0.004370096
0.000663018
0.73639502
0.000215874


rc_AA402468_at
261
AA402468

0.099732216
9.36987E−05
0.673315411
0.017152495
0.245352826
0.000668187


rc_AA402473_at
262
AA402473

0.457960224
0.000426525
0.079152517
6.26915E−05
0.336346183
1.26194E−06


rc_AA405331_at
267
AA405331
golgi autoantigen, golgin subfamily a, 5
0.586184325
0.001885183
0.429082537
0.000584353
0.815182938
0.00026866


rc_AA405533_at
269
AA405533
integral membrane protein 2B
0.000172614
0.497994468
0.082141472
0.000159183
0.055604922
0.0359498


rc_AA405902_at
272
AA405902

0.086820061
0.039035914
0.014052865
0.000655228
0.480598833
5.66656E−05


rc_AA410954_at
279
AA410954

1.16178E−05
1.50623E−06
1.03048E−05
0.330330235
0.980294091
0.341205824


rc_AA411897_at
281
AA411897

0.508186682
0.001994491
0.445499823
0.00043102
0.923458644
0.000312647


rc_AA412267_at
286
AA412267

0.164103629
3.89169E−07
0.756068057
1.61111E−09
0.10637429
3.90003E−06


rc_AA412443_at
287
AA412443

0.364026646
0.005904843
0.355261504
0.000673161
0.987349969
0.000639721


rc_AA417011_at
292
AA417011

0.97881335
0.000103601
0.347607058
0.000209225
0.359543109
6.44615E−06


rc_AA417348_at
293
AA417348

0.011726682
0.000513628
0.000733098
0.214868351
0.416407972
0.597824364


rc_AA417915_at
294
AA417915

0.00031475
0.724609869
0.33434685
0.000849216
0.012345648
0.253561808


rc_AA418557_at
295
AA418557

0.228039568
0.580130356
0.000535144
0.124915173
0.032252409
0.000643742


rc_AA421131_at
298
AA421131

0.000944552
0.385647564
0.015545606
0.00033745
0.400009139
0.00441922


rc_AA421133_at
299
AA421133
erythrocyte transmembrane protein
0.048370115
0.776945443
3.5594E−06
0.170573072
0.011573179
0.000337276


rc_AA424037_s_at
301
AA424037

0.004243716
0.739593135
2.30322E−05
0.006963992
0.192467998
0.000122214


rc_AA424245_at
302
AA424245

0.000912849
0.241386195
0.000608875
0.10233451
0.915105608
0.08414343


rc_AA424515_at
303
AA424515

0.001461647
0.327161944
0.557700471
0.000331758
0.000350136
0.650111174


rc_AA425325_at
305
AA425325

0.000137613
0.761000474
0.006888125
0.000531496
0.292230161
0.011066086


rc_AA425354_at
306
AA425354

1.135E−05
0.848812392
4.31696E−05
0.000125249
0.776028887
0.000335665


rc_AA426438_at
309
AA426438
tissue factor pathway inhibitor (lipoprotein-
0.086215951
0.051460629
0.077775438
0.000971113
0.963651921
0.000841613





associated coagulation inhibitor)


rc_AA426454_s_at
310
AA426454
imidazoline receptor candidate
4.93792E−06
0.168883843
0.000430545
0.013194044
0.320673843
0.1079437


rc_AA427944_at
313
AA427944

0.016580683
2.63482E−05
0.961128446
0.040898728
0.020386125
4.53083E−05


rc_AA428243_at
314
AA428243
integrin beta 4 binding protein
0.000258966
0.030169371
0.000115376
0.338639919
0.847641147
0.260434676


rc_AA428460_at
316
AA428460

0.369406205
2.86818E−05
0.170103625
1.87552E−06
0.031318989
0.00400089


rc_AA429398_s_at
317
AA429398

0.042509423
0.318204908
0.000808205
0.00812556
0.209966492
0.000179435


rc_AA430738_at
322
AA430738
hypothetical protein FLJ22693
2.4223E−05
0.512347676
0.057495876
3.43792E−05
0.027579258
0.027106503


rc_AA433922_at
326
AA433922
NRAS-related gene
0.000129534
0.750927276
0.024589837
0.000483913
0.13400345
0.02912486


rc_AA435753_at
329
AA435753

0.167368191
0.01678153
0.00563702
0.000567982
0.188083313
4.20658E−06


rc_AA435852_at
331
AA435852
hypothetical protein
0.000178813
0.813799408
0.130706548
0.000825341
0.033909282
0.137866512


rc_AA436244_at
332
AA436244

0.000347902
0.773066458
0.838936155
0.006955308
0.000335763
0.655473596


rc_AA436489_at
333
AA436489
dual specificity phosphatase 10
0.089585972
0.000336423
0.53802583
0.042116461
0.028187175
7.58265E−05


rc_AA436548_at
334
AA436548

4.79946E−05
0.79712195
0.073989554
0.000284052
0.03065051
0.082990101


rc_AA436823_at
338
AA436823

3.43729E−06
0.007238466
0.000134014
0.199586541
0.434475995
0.550333062


rc_AA436841_at
339
AA436841
nuclear factor of kappa light polypeptide gene
0.000757034
0.109130693
3.14861E−05
0.206545207
0.451070087
0.054341855





enhancer in B-cells inhibitor, beta


rc_A437226_s_at
341
AA437226
interleukin 10 receptor, alpha
0.030634205
0.394007384
3.12463E−06
0.008853685
0.017676075
2.623E−06


rc_AA442830_at
342
AA442830

0.277387057
0.000957882
0.739163222
4.56542E−05
0.474861158
0.000560401


rc_AA446899_at
348
AA446899
mannosidase, alpha, class 1B, member 1
4.08376E−08
0.474845978
8.66417E−09
0.000104871
0.799444331
4.09828E−05


rc_AA448228_at
353
AA448228
HSPC142 protein
0.489815716
0.427628808
0.00011718
0.181303904
1.63664E−05
0.014570459


rc_AA450073_s_at
357
AA450073
paired mesoderm homeo box 1
0.070060208
0.424331633
0.00057893
0.02291416
0.12207024
0.000282414


rc_AA450373_at
361
AA450373

0.19184076
0.000421707
3.75092E−05
0.021344923
0.007526828
0.966348045


rc_AA454016_at
365
AA454016

0.74223808
0.000765848
0.794392558
0.003084476
0.575990681
0.000561238


rc_AA454928_at
367
AA454928
phosphorylase kinase, beta
0.042150436
0.023733581
0.157838834
0.000111797
0.556629171
0.000814363


rc_AA457148_at
372
AA457148

0.770822781
0.643699605
7.37551E−05
0.492232725
0.000493842
0.00082201


rc_AA457407_at
374
AA457407
transmembrane protease, serine 2
0.322389783
0.009487182
0.088848624
0.000914536
0.499415786
9.30818E−05


rc_AA457675_at
376
AA457675

0.000470812
0.007879992
0.000974653
0.721378015
0.850190113
0.848554875


rc_AA459272_at
377
AA459272

8.59013E−05
0.738589634
0.711426345
0.003207799
0.00073865
0.989771621


rc_AA460377_at
378
AA460377
beta-catenin-interacting protein ICAT
0.015059101
0.036482503
0.009644184
5.52729E−05
0.881315511
3.13984E−05


rc_AA464598_at
387
AA464598
KIAA1389 protein
0.000373603
0.650628457
0.000200085
0.000684765
0.878718031
0.000416438


rc_AA469954_at
392
AA469954

0.239197445
0.004848961
0.288136551
0.000228067
0.913292289
0.000330413


rc_AA476594_i_at
393
AA476594
Arg/Abl-interacting protein ArgBP2
0.358342961
0.881892103
0.000846963
0.534258655
5.41111E−05
0.003508506


rc_AA477119_at
395
AA477119

0.155425839
0.46185093
0.00021398
0.058896186
0.030447512
0.000152407


rc_AA477833_at
397
AA477833
translocase of inner milochondrial membrane
0.019542745
0.5471713
3.40147E−05
0.011694366
0.085999006
5.64814E−05





44 (yeast) homolog


rc_AA478615_s_at
398
AA478615
H1 histone family, member X
0.640957846
0.0022057
0.208838599
0.000871626
0.453348417
6.70146E−05


rc_AA478996_at
401
AA478996

0.680984202
0.000380025
0.977809564
0.000172484
0.677109345
0.000696316


rc_AA481057_f_at
404
AA481057

0.029606002
0.060557911
0.05307758
0.000302603
0.819130316
0.000643675


rc_aa482107_s_at
406
AA482107

0.412141577
0.217724563
0.000197553
0.061952573
1.63874E−05
0.055779976


rc_AA482559_at
407
AA482559
RPA-binding transactivator
0.010341566
0.960676267
3.22844E−05
0.02919031
0.130837801
0.000454944


rc_AA485243_at
408
AA485243
leptin receptor
3.17405E−05
0.744743793
0.400224468
0.00016024
0.001638049
0.311163055


rc_AA488658_at
413
AA488658
hypothetical protein
0.000418682
0.365249562
0.186392502
0.000141589
0.036308821
0.048918937


rc_AA488849_at
414
AA488849
nucleotide binding protein 2 (E.coli MinD like)
0.17603882
0.323192094
0.000687853
0.037989302
0.052798072
0.000161003


rc_AA489637_at
415
AA489637

0.003960452
0.871859148
0.000107388
0.010699848
0.346672042
0.000730896


rc_AA490120_at
416
AA490120

0.082001486
0.454413511
0.000859271
0.030324764
0.130537834
0.000479561


rc_AA490520_at
418
AA490520

0.00063489
0.471991068
0.445872157
0.000410063
0.011810787
0.185068096


rc_AA490999_at
420
AA490999

0.001846648
0.670951196
0.000150658
0.002708195
0.521238606
0.000368557


rc_AA504255_at
423
AA504255
ataxia telangiectasia and Rad3 related
0.007747725
1.58087E−05
0.446946913
0.053347131
0.001163384
1.74835E−06


rc_AA505022_at
425
AA505022

0.250524892
0.000259519
0.084574205
7.98938E−06
0.584980634
7.63588E−07


rc_AA599376_at
435
AA599376

0.015748126
0.140670046
0.009272938
0.000615583
0.859099543
0.000343134


rc_AA599443_f_at
436
AA599443
hypothetical protein FLJ10595
0.379179145
0.00382066
0.40828628
0.000446702
0.960279666
0.000525999


rc_AA609657_at
446
AA609657

7.04465E−05
0.091053447
0.00093271
0.092251403
0.5283101
0.25823308


rc_AA609848_at
447
AA609848

0.042723584
0.092999102
0.036171711
0.000967007
0.948118344
0.000787862


rc_AA609869_at
448
AA609869
hypothetical protein FLJ13222
4.47677E−05
0.00053907
2.12675E−07
0.943295205
0.293840522
0.321292026


rc_AA610070_at
450
AA610070
calcium/calmodulin-dependent serine protein
0.000126016
0.058243496
0.558814317
0.170494931
2.76548E−05
0.021111632





kinase (MAGUK family)


rc_AA620806_at
453
AA620806
ASB-3 protein
4.7861E−06
0.710135071
0.298838834
0.000563366
0.000797621
0.611912234


rc_AA621325_at
455
AA621325
HNK-1 sulfotransferase
0.000848661
0.346193012
0.004864951
0.000232221
0.621405553
0.001162331


rc_C14898_at
467
C14898

0.000226586
0.885711705
6.82551E−05
0.003389818
0.77964221
0.001496457


rc_C20547_at
469
C20547

0.068260402
0.000952953
0.812550962
2.71206E−06
0.132387942
0.000746928


rc_C20658_at
470
C20658
cisplatin resistance-associated overexpressed protein
0.000322792
0.311886375
0.000285103
7.37384E−05
0.975640568
6.58868E−05


rc_D11789_f_at
473
D11789

0.21798848
0.000243771
0.79113972
0.012426673
0.155631425
0.000180292


rc_D11961_at
475
D11961
hypothetical protein FLJ21343
0.066999427
0.031322113
0.050959636
0.000327468
0.909256528
0.000222056


rc_D20085_at
479
D20085

0.533566658
0.000441315
0.321182892
0.004260671
0.125585439
2.65015E−05


rc_D52692_s_at
497
D52692
Ca2+-dependent activator protein for secretion
1.02115E−06
0.807110908
1.27404E−05
0.000127062
0.619779281
0.000681487


rc_D60272_i_at
499
D60272

0.000665091
0.000166097
0.000151004
0.431868883
0.714339713
0.641956827


rc_D80298_f_at
507
D80298

0.045427886
0.000323207
0.958861584
0.073418502
0.064448036
0.000644976


rc_D80738_f_at
509
D80738

0.190797369
0.00173762
0.245104642
4.17807E−05
0.889912758
7.00818E−05


rc_F01684_at
519
F01684

0.420181016
0.000494834
0.488322276
5.87948E−05
0.914533384
8.72831E−05


rc_F02739_at
525
F02739

5.54856E−05
0.053527575
0.000291424
0.133799091
0.698411971
0.246269511


rc_F04019_at
529
F04019

0.000166861
0.000950517
0.555841593
0.965823573
0.00259065
0.007252422


rc_F10193_at
539
F10193
chromosome 21 open reading frame 39
1.30777E−05
0.948962688
0.020624022
0.000363518
0.05248761
0.062247376


rc_F10323_f_at
540
F10323
retinoblastoma-like 2 (p130)
0.000650946
0.502771636
0.015425251
0.000500148
0.348990394
0.007831047


rc_F10980_at
541
F10980

8.9375E−05
0.653407439
0.012465868
0.000223205
0.178217348
0.012058063


rc_H01068_at
543
H01068

0.86517363
0.000569676
0.466764828
0.001528575
0.394499429
9.00281E−05


rc_H09077_at
551
H09077

3.06359E−05
1.2292E−05
0.021919052
0.46401342
0.07497746
0.021793621


rc_H11463_at
552
H11463
inhibitor of growth family, member 3
0.00061851
0.000440258
0.000113152
0.597222623
0.678354487
0.869200328


rc_H14810_s_at
553
H14810
popeye protein 3
1.36532E−05
0.832182578
0.004057496
0.000637115
0.161519166
0.028710637


rc_H18099_at
560
H18099

0.247088588
0.003400663
0.301565366
0.000158641
0.90607919
0.000239103


rc_H23407_s_at
565
H23407
MAD1 (mitotic arrest deficient, yeast,
0.000753122
0.112093793
2.71462E−05
0.201584279
0.432877141
0.049424886





homolog)-like 1


rc_H23520_at
566
H23520

0.611355729
0.000871266
0.849483973
0.000293132
0.507906287
0.002361124


rc_H38418_at
570
H38418

0.185134143
0.065592241
0.008782561
0.50515013
0.000181804
7.8388E−05


rc_H38995_f_at
571
H38995
KIAAO471 gene product
0.009631356
0.97045862
5.86902E−05
0.028554385
0.175136692
0.000728104


rc_H45265_at
574
H45265
ATP-binding cassette, sub-family A (ABC1), member 7
0.000152193
4.19671E−07
0.003258301
0.08727525
0.422648726
0.015812939


rc_H48263_at
575
H48263

0.185258234
0.007096561
0.191295818
0.00022522
0.986389253
0.000238835


rc_H48475_at
576
H48475
ribosomal protein L37a
0.227463546
0.00062116
0.579381783
1.76941E−05
0.535824365
0.000177441


rc_H58781_at
582
H58781

0.042650671
0.000369904
0.497627082
0.082860732
0.010272658
6.73936E−05


rc_H59141_at
584
H59141
hypothetical protein
0.001248184
4.64747E−07
0.066732688
0.031003204
0.185961631
0.000909745


rc_H63994_at
588
H63994

0.042052556
0.003078049
0.051932289
5.75286E−06
0.93248223
8.15902E−06


rc_H64411_at
589
H64411
KIAA0618 gene product
0.01802462
0.070417348
0.012928934
0.000210449
0.908905166
0.000140956


rc_H77531_s_at
593
H77531
HIR (histone cell cycle regulation defective, S.
0.000791123
0.49434307
0.184056577
0.00056294
0.054421223
0.078090378





cerevisiae) homolog A


rc_H97868_at
608
H97868

0.322057918
0.489184724
0.000285548
0.136645099
0.012333089
0.000230315


rc_H97889_at
609
H97889

0.158642014
0.00916284
0.299358664
0.000236375
0.724266848
0.00075937


rc_H98676_at
610
H98676

0.127756769
0.002896791
0.262913685
3.64577E−05
0.701889069
0.000148754


rc_N20967_at
717
N20967

9.92879E−05
0.817666422
3.00688E−05
0.000539948
0.790070901
0.000221099


rc_N22115_s_at
720
N22115
KIAA0447 gene product
5.18274E−07
0.014513808
3.98659E−05
0.067547386
0.387363889
0.284673955


rc_N22297_f_at
721
N22297

0.054494667
0.052949003
0.08027668
0.000541487
0.869037035
0.000917296


rc_N32521_at
735
N32521
hypothetical protein FLJ11085
0.547891484
0.041933612
0.000238523
0.014113039
0.003549591
5.39907E−07


rc_N34517_s_at
738
N34517
integrin, alpha 7
0.005879801
0.196182153
0.004385481
0.00040993
0.928485921
0.000303466


rc_N38882_at
741
N38882

0.014629787
0.005666897
0.251351421
0.530957263
0.000663242
0.000303436


rc_N51579_at
748
N51579
transporter-like protein
0.44766874
6.17952E−05
0.962144968
0.001295779
0.499475206
0.00139415


rc_N54053_at
752
N54053
secreted phosphoprotein 2, 24 kD
0.116492665
0.015273471
0.039361645
0.00027615
0.641546757
5.23218E−05


rc_N54845_at
753
N54845

0.000443555
0.073889565
0.000793416
0.227981278
0.881125278
0.282635582


rc_N55085_at
754
N55085

0.220208071
0.876075911
0.000843717
0.384166413
1.49242E−05
0.003419797


rc_N59862_at
760
N59862

0.462122243
0.001300248
0.276791676
0.000214232
0.741521525
6.58223E−05


rc_N66001_at
765
N66001
mouse double minute 4,human homolog of; p53-
0.269409972
0.001627722
0.449591713
7.93964E−05
0.741058833
0.000255792





binding protein


rc_N66053_f_at
766
N66053
butyrophilin, subfamily 3, member A1
0.000767668
0.638609685
0.000120387
0.018876455
0.648066184
0.005990603


rc_N67108_at
769
N67108

2.22447E−05
0.94547199
0.335823565
0.000534028
0.00186846
0.462281008


rc_N67324_at
770
N67324

0.061297249
0.015332682
0.029486337
0.000101757
0.771895611
3.46367E−05


rc_N67899_at
774
N67899

8.19817E−05
0.845939057
0.027139019
0.000532728
0.100944503
0.04285656


rc_N80693_at
787
N80693

0.798568519
0.000819546
0.654401168
0.002677747
0.504907369
0.000334108


rc_N89827_at
788
N89827
RALBP1 associated Eps domain containing 2
0.129696038
0.000403735
8.58239E−05
0.032513633
0.022112053
0.895818166


rc_N93495_at
795
N93495
uncharacterized hematopoietic
0.082365924
0.047090947
0.00063645
0.000799522
0.111310122
2.03892E−06





stem/progenitor cells protein MDS033


rc_R00440_at
802
R00440
ancient conserved domain protein 4
0.538637852
6.90248E−05
0.927092838
0.000926675
0.619532275
0.000178704


rc_R17000_s_at
812
R17000
NADH dehydrogenase (ubiquinone) Fe—S protein 8
0.000151792
0.075089669
0.000101925
0.149353698
0.926045731
0.12770179





(23 kD) (NADH-coenzyme Q reductase)


rc_R25116_at
813
R25116

0.0420832
0.03125809
0.026701279
0.000169518
0.862052816
9.11635E−05


rc_R40030_at
827
R40030
hypothetical protein FLJ20047
0.567472456
0.000280009
0.804462147
0.002571098
0.436977215
0.000218515


rc_R41798_s_at
829
R41798
KIAA1374 protein
0.000373432
0.706910506
0.012448736
0.000894251
0.315054178
0.014659398


rc_R42336_s_at
831
R42336

0.70873782
2.16988E−05
0.77916386
0.000163747
0.929588049
0.000119701


rc_R42525_at
833
R42525

0.050001405
0.071849508
0.013930003
0.000778775
0.635857474
0.000159677


rc_R56216_at
845
R56216

0.000821825
0.352494161
0.151440792
0.0002362
0.069860079
0.036903476


rc_R66690_at
851
R66690

0.548034357
0.001498849
0.392082801
0.000384981
0.808745096
0.000168251


rc_R702125_s_at
853
R70212

0.001627385
0.92358255
1.96242E−05
0.011419498
0.28878538
0.000540241


rc_R82942_s_at
856
R82942

4.27278E−06
0.038346252
9.40527E−05
0.06641734
0.511382181
0.207797821


rc_R84968_at
858
R84968

0.029165843
9.17654E−05
0.74623486
0.052010697
0.078018241
0.0004854


rc_R89291_at
861
R89291

0.000287625
0.129809655
0.120359785
7.72734E−06
0.049234398
0.005999323


rc_R92737_at
864
R92737
aquaporin 3
0.045317535
0.54600908
0.000762777
0.024731156
0.195577177
0.000722979


rc_T15530_at
879
T15530

0.039751248
0.193908111
0.000219396
0.003085344
0.119916961
1.53896E−05


rc_T16556_at
882
T16556

0.547027876
0.000735355
0.131501406
0.006096912
0.045271057
6.8433E−06


rc_T49291_s_at
895
T49291
lymphocyte-specific protein 1
0.023580272
0.159004442
0.000765019
0.00120856
0.296144015
3.27932E−05


rc_T50387_at
897
T50387

0.685476265
0.000770227
0.324729565
0.003799426
0.187347142
5.10594E−05


rc_T53404_at
898
T53404
hypothetical protein from clone 643
0.47780256
0.003673041
0.259379562
0.000720609
0.69168737
0.000191916


rc_T54613_at
900
T54613

5.52684E−05
0.022747185
0.000284729
0.24335011
0.701984774
0.40594297


rc_T54617_at
901
T54617

0.857947447
4.07249E−05
0.397904433
0.000146584
0.527265593
0.001199664


rc_T65802_at
908
T65802

0.012663512
0.532196596
0.000313482
0.007483397
0.291974796
0.000319721


rc_T79868_f_at
915
T79868
hypothetical protein 384D8_6
0.071499128
0.033264086
0.074047238
0.000392669
0.987909984
0.000412941


rc_T82292_s_at
916
T82292
protease, serine, 11 (IGF binding)
0.000399556
0.678142361
0.051597503
0.000824339
0.130506724
0.043561586


rc_T86121_at
918
T86121

0.013631945
0.898945913
2.7658E−06
0.029665506
0.035142628
5.76483E−05


rc_T87533_at
920
T87533

0.989160192
0.000472522
0.640089183
0.000751611
0.648053004
0.002981136


rc_T90038_f_at
924
T90038
butyrophilin, Subfamily 3, member A2, butyrophilin,
4.93914E−06
0.243601757
8.38948E−05
0.007362582
0.547300658
0.031384668





subfamily 3, member A3


rc_T99373_at
934
T99373

0.026021837
3.07604E−06
0.711043501
0.008523742
0.078371167
2.98773E−05


rc_W37384_i_at
1001
W37384
non-metastatic cells 5, protein expressed in
0.000625839
0.217732697
0.000147234
0.096608548
0.7216482
0.048383963





(nucleoside-diphosphate kinase)


rc_W42483_at
1003
W42483
hypothetical protein similar to mouse Dnajl1
2.97466E−05
0.676684762
0.031770051
0.000106724
0.05435082
0.028721568


rc_W44558_s_at
1005
W44558
adaptor-related protein Complex 1, sigma 1 subunit
0.079864992
0.042988764
0.034848175
0.000669599
0.73367308
0.000215475


rc_W60649_at
1019
W60649

0.023339325
0.129224665
0.006757142
0.000824018
0.675851904
0.000206179


rc_W80509_s_at
1032
W80509
death associated transcription factor 1
0.000271744
0.148661601
0.000426903
0.10048575
0.910884693
0.122505852


rc_W86660_at
1034
W86660

0.150249394
6.18841E−06
0.557722374
0.001658036
0.418699422
0.000115844


rc_W93396_at
1038
W93396

0.000180228
0.540603359
0.319667744
0.00021213
0.009081674
0.156804025


rc_Z38551_s_at
1107
Z38551
hypothetical protein FLJ10210
0.007617909
0.125060522
0.00394587
0.000220695
0.839190935
0.000107925


rc_Z39874_at
1110
Z39874

0.018342738
0.000251552
0.969844211
0.120049181
0.022998914
0.000387407


rc_Z40012_f_at
1113
Z40012
NCK-associated protein
0.038639336
0.043854062
0.05138364
0.000255085
0.909554475
0.000374451


rc_Z40332_at
1115
Z40332
vesicle docking protein p115
0.028012659
0.10943539
0.012529791
0.000762549
0.7761268
0.000299824


rc_Z41763_at
1120
Z41763

6.03127E−05
0.82776366
0.002670862
0.00038983
0.338788944
0.006770727


S75463_at
871
S75463
Tu translation elongation factor, mitochondrial
0.000271911
0.000533911
0.00172916
0.765671272
0.63019533
0.471338415


S77154_s_at
872
S77154
nuclear receptor subfamily 4, group A, member 2
0.720602576
0.932154297
5.84424E−05
0.829150677
0.000513773
0.001105408


T40327_s_at
891
T40327
electron-transferring-flavoprotein dehydrogenase
7.27596E−06
0.215221988
0.819260055
0.011040692
7.74754E−06
0.167330005


T89243_s_at
922
T89243
KIAA1243 protein
0.00081408
0.517949226
0.114764867
0.000657245
0.092965856
0.053186849


U00672_at
935
U00672
interleukin 10 receptor, alpha
0.000287943
0.609290849
1.66617E−06
0.011540026
0.269359727
0.000474683


U03272_at
937
U03272
fibrillin 2 (congenital contractural arachnodactyly)
0.000310928
0.332521737
0.209649826
8.44451E−05
0.025692948
0.04828388


U04811_at
939
U04811
trophinin
1.5625E−05
0.755433375
0.054905474
0.000984445
0.022792101
0.194301082


U04811_at
939
U04811
trophinin
2.20509E−06
0.327834193
0.000136465
0.002712738
0.383208442
0.025499623


U09366_at
943
U09366
zinc finger protein 133 (clone pHZ-13)
0.000213171
0.5068558
0.610828511
0.000200267
0.002444941
0.288631384


U11861_at
945
U11861
maternal G10 transcript
0.000482828
0.00167301
9.90184E−05
0.90794872
0.702310162
0.826191525


U12775_at
946
U12775
agouti (mouse)-signaling protein
0.000271316
0.000844452
0.000473875
0.859392382
0.889729458
0.765131751


U13220_at
947
U13220
forkhead box F2
0.000592743
0.851887641
3.88357E−05
0.007392289
0.519237
0.001178975


U13991_at
948
U13991
TATA box binding protein (TBP)-associated factor,
1.45014E−06
0.006140037
1.01255E−06
0.168790439
0.946149483
0.151190281





RNA polymerase II, H, 30 kD


U15932_at
949
U15932
dual specificity phosphatase 5
0.877505283
0.806495835
1.85723E−05
0.914714787
2.57739E−05
0.000146058


U23852_s_at
954
U23852
lymphocyte-specific protein tyrosine kinase
0.015926444
0.891018698
9.08522E−05
0.032567274
0.153847965
0.000703723


U25265_at
957
U25265
mitogen-activated protein kinase kinase 5
8.86395E−06
0.005417963
5.93432E−05
0.305372601
0.684875389
0.503461673


U26174_at
959
U26174
granzyme K (serine protease, granzyme 3, tryptase II)
3.92686E−05
0.206902143
0.000598254
0.027205202
0.519267093
0.10031708


U32674_s_at
962
U32674
G protein-coupled receptor 9
0.003147245
0.1818672
0.076391484
0.000184255
7.37649E−06
0.847933992


U40372_at
963
U40372
phosphodiesterase 1C, calmodulin-dependent (70 kD)
0.284766484
1.17113E−05
0.46702597
0.000897191
0.745348724
0.000311221


U43527_at
966
U43527
KiSS-1 metastasis-suppressor
0.068750933
0.878566298
0.000141006
0.096679594
0.059509384
0.000920023


U46006_s_at
968
U46006
cysteine and glycine-rich protein 2
0.000581958
0.677096089
0.000421368
0.013813896
0.93464395
0.011277242


U52112_ma1_at
969
U52112
L1 cell adhesion molecule (hydrocephalus, stenosis of
0.012256648
0.603209864
0.000361314
0.009782964
0.313616052
0.000525936





aqueduct of Sylvius 1, MASA (mental retardation, aphasia,





Shuffling gait and adducted thumbs) syndrome, spastic





paraplegia 1)


U55209_at
973
U55209
myosin VIIA (Usher syndrome 1B (autosomal recessive,
0.026307797
0.000534284
5.50778E−05
0.139252083
0.085728294
0.977237559





severe))


U57623_s_at
975
U57623
fatty acid binding protein 3, muscle and heart
0.000249597
0.006076702
2.31411E−07
0.680669423
0.152138423
0.095412354





(mammary-derived growth inhibitor)


U58522_at
976
U58522
huntingtin interacting protein 2
0.950874668
0.000404266
0.026015373
0.000816174
0.04004298
0.12201215


U66075_at
980
U66075
GATA-binding protein 6
0.000177786
0.094949773
5.41966E−05
0.129840147
0.784613111
0.079354568


U66615_at
981
U66615
SWI/SNF related, matrix associated, actin
0.00427057
0.860602352
0.000125812
0.01088834
0.353965999
0.000781605





dependent regulator of chromatin, subfamily c, member 1


U89922_s_at
987
U89922
lymphotoxin beta (TNF superfamily, member 3)
0.081431989
0.705262065
1.14225E−05
0.069803458
0.012069263
5.95219E−05


W52493_at
1013
W52493

4.17744E−05
0.407939223
0.47764998
2.61848E−05
0.001311163
0.165780725


X06318_at
1048
X06318
protein kinase C, beta 1
4.53981E−05
0.309598889
0.000193355
0.01564851
0.739435449
0.033561473


X07315_at
1053
X07315
nuclear transport factor 2 (placental protein 15)
0.00096734
0.024484461
0.000991289
0.558914618
0.994799819
0.56276584


X14008_rna1_f_at
1056
X14008
lysozyme (renal amyloidosis)
0.047298803
0.921767172
1.2563E−05
0.081015792
0.023720356
0.000192698


X14046_at
1057
X14046
CD37 antigen
0.032116442
0.896768704
6.54708E−06
0.097237805
0.024859085
0.000287679


X14830_at
1058
X14830
cholinergic receptor, nicotinic, beta polypeptide 1 (muscle)
0.936178672
0.000286907
0.137976127
0.000630986
0.183095639
0.024428637


X16316_at
1059
X16316
vav 1 oncogene
0.005646314
0.4794965
0.000157845
0.002861938
0.337620027
0.00013174


X54870_at
1065
X54870
DNA segment on chromosome 12 (unique) 2489 ex-
0.000450913
0.241248516
0.00029577
0.07293822
0.916408
0.059393045





pressed sequence


X58529_at
1070
X58529
immunoglobulin heavy constant mu
0.026942297
0.975028968
5.32141E−08
0.070184957
0.002196974
6.90925E−06


X60673_s_at
1072
X60673
adenylate kinase 3
0.014055428
1.64563E−05
0.000854329
0.036097108
0.40449053
0.17235001


X63741_s_at
1074
X63741
early growth response 3
0.050166995
0.302932401
1.63652E−08
0.522269647
0.000467351
0.000208487


X66358_at
1079
X66358
cyclin-dependent kinase-like 1 (CDC2-related kinase)
3.6744E−05
0.079324094
3.35901E−05
0.080441339
0.984409054
0.077518373


X66839_at
1080
X66839
carbonic anhydrase IX
3.93574E−06
0.662915937
0.008885816
0.000624117
0.057988735
0.078713562


X68277_at
1082
X68277
dual specificity phosphatase 1
0.003463894
0.023542489
5.00933E−13
0.79747022
4.48312E−05
0.000125081


X72882_at
1084
X72882

0.000586574
1.73881E−05
0.061863645
0.20511364
0.136254698
0.010057929


X75962_at
1085
X75962
hypothetical protein FLJ10747,tumor necrosis
1.07753E−05
0.259082214
0.000322398
2.07333E−06
0.445393473
4.56511E−05





factor receptor superfamily, member 4


X83705_s_at
1089
X83705
platelet-derived growth factor beta polypeptide
0.000211219
0.000641028
0.003169595
0.843987656
0.474177301
0.409652768





(simian sarcoma viral (v-sis) oncogene homolog)


X96584_at
1096
X96584
nephroblastoma overexpressed gene
0.000449835
0.36091834
0.013539811
0.00014621
0.323949108
0.003364493


X99142_at
1097
X99142
keratin, hair, basic, 6 (monilethrix)
0.104620098
0.022019682
0.075077447
0.00038452
0.881497721
0.000232112


Y07595_at
1099
Y07595
general transcription factor IIH, polypeptide 4
0.000268402
0.028695565
5.26844E−05
0.352269642
0.704788647
0.206775434





(52 kD subunit)


Y09022_at
1102
Y09022
Not56 (D. melanogaster)-like protein
0.000142024
0.084289616
0.000108418
0.131801466
0.949831739
0.118236485


Z35093_at
1105
Z35093
surfeit 1
0.000740458
0.015177247
0.000173743
0.635076989
0.718277145
0.428942461



















TABLE 7









Prostatic
Cell Line













tissues
BRF-55T
PZ-HPV7
BPH-1
LNCaP
















Up-regulated
 61
33
22
20
20


genes


Down-regulated
 43
31
28
30
33


genes


Total
104
64
50
50
53

## Claims

1. A computer system comprising:
(a) a processor; and
(b) a computer readable storage medium storing executable instructions that, when executed by the processor, cause the processor to perform a plurality of steps, wherein the steps include:
(i) comparing an expression profile of a test sample from a subject to a reference expression profile, wherein the expression profile of the test sample comprises statistical measures of differential expression of two or more nucleic acid sequences selected from SEQ ID NO: 1 to 1124 in the test sample as compared to a control sample from a normal individual and the reference expression profile comprises statistical measures of differential expression of said two or more nucleic acid sequences in a individual diagnosed with benign prostatic hyperplasia (BPH) as compared to a normal individual; and
(ii) identifying the presence or absence of BPH in the subject, wherein differential expression of said two or more nucleic acid sequences in the test sample is indicative of BPH.

2. The computer system of claim 1, wherein the expression profile of the test sample comprises statistical measures of differential expression of 10 or more nucleic acid sequences selected from SEQ ID NO: 1 to 1124.

3. The computer system of claim 1, wherein the expression profile of the test sample comprises statistical measures of differential expression of each of SEQ ID NO: 1 to 1124.

4. The computer system of claim 1, further comprising records including information from an external database, which information correlates said nucleic acid sequences to records in said external database.

5. The computer system of claim 1, wherein the reference gene expression profile is part of a database.

6. The computer system of claim 5, wherein the database further comprises nucleotide sequence information for said nucleic acid sequences.

7. The computer system of claim 6, wherein said database further comprises descriptive information about said nucleic acid sequences.

8. The computer system of claim 5, wherein said database further comprises descriptive information from the subject.

9. The computer system of claim 8, wherein said descriptive information is selected from the group consisting of subject age, disease status and treatment status.

10. The computer system of claim 9, wherein said disease status information comprises prostate specific antigen (PSA) serum level values.

11. The computer system of claim 9, wherein said disease status information comprises information related to disease progression.

12. A computer system comprising:
(a) a processor; and
(b) a computer readable storage medium storing executable instructions that, when executed by the processor, cause the processor to perform a plurality of steps, wherein the steps include:
(i) comparing an expression profile of a test sample from a subject to a reference expression profile, wherein the expression profile of the test sample comprises statistical measures of differential expression of five or more nucleic acid sequences selected from SEQ ID NO: 1 to 1124 in the test sample as compared to a control sample from a normal individual and the reference expression profile comprises statistical measures of differential expression of said five or more nucleic acid sequences in a individual diagnosed with benign prostatic hyperplasia (BPH) as compared to a normal individual; and
(ii) identifying the presence or absence of BPH in the subject, wherein differential expression of said five or more nucleic acid sequences in the test sample is indicative of BPH.