PATENT ABSTRACT
A method of predicting the development of a cancer in a patient, comprises procuring a sample of tumour tissue from the patient, determining the expression pattern of embryonic stem cell genes in the tissue, comparing the expression pattern with the corresponding expression pattern of embryonic stem cell genes in tumour tissue of reference patients with known disease histories. Also disclosed are microarrays and DNA/RNA probes for use in the method.

PATENT DESCRIPTION
FIELD OF THE INVENTION 
       [0001]    The present invention relates to embryonic stem cell (ES) gene markers for use in diagnosis and prognosis of cancer, in particular prostate cancer. 
       BACKGROUND OF THE INVENTION 
       [0002]    Gene expression profiling in cancer cells of various kind as well as in embryonic stem (ES) cells using high throughput DNA microarrays is known in the art. A direct link between tumor and ES cell expression signatures has however not been established. 
         [0003]    Bioinformatic analyses based on published or unpublished high throughput proteomic data have not yet reached robust and high resolution as compared with high throughput DNA and RNA analyses. Bioinformatic analyses based on published and unpublished high throughput genome-scale DNA analyses provide a list of DNA markers in the form gene copy number changes (deletions, gains and amplifications), mutations and polymorphisms, and methylations. DNA is comparatively stable and easy to be handled in analytical process. However, these DNA changes have to be detected by different methods. 
         [0004]    It is still an open question why cancer originating from the same kind of tissue progresses slowly in one person and rapidly in another. Recent expression profiling analyses have provided quite complete and specific molecular portraits of many cancers, especially of subtypes of a particular cancer differing in clinical outcome (1-4). Some studies even provided short lists of genes, the expression of which is predictive of the outcome of the respective cancer (5-6). These expression profiling results have led to further functional studies of selected markers or genes (7). However, in general, the selection of “important” genes is based on a pure statistical approach (8-9). Despite many new theories and methods trying to coup with the challenge of huge amounts of data-provided by high throughput experiments, the statistics in this field is still very much under development. Most studies therefore turn into a lottery from a list of “markers”, and their result is largely confined to a molecular phenotypic level (10). 
         [0005]    Prostate cancer is a major cause of death worldwide in male adults. Accurately predicting the outcome of prostate cancer at an early stage of tumor development is crucial for providing the proper kind of treatment, and is still an unresolved question. The correct choice of treatment is most important in younger patients (11). It is estimated that of 232,090 American men with newly diagnosed prostate cancer in 2005, roughly 210,000 or approximately 90% will be diagnosed at an early stage with 100% survival for 5 years. In contrast, the estimated deaths from prostate cancer are much less, about 30,350 (12). Online data from the Swedish National Board of Health and Welfare have shown that 7,702 out of 4,427,107 Swedish men in 2001 had newly diagnosed prostate cancer. In a randomized clinical observation of 348 patients with early stage and well to moderately-well differentiated prostate cancer, 108 (31%) showed local progression, 54 (15.5%) had distant metastases and only 31 (8.9%) had deceased from prostate cancer after 8 years follow-up (13). Some early stage prostate cancers can be indolent during 8 years of follow-up and display accelerated progression later after a follow-up of more than 15 years. However, these late-progressive tumors only constitute up to 17% of all early stage cases (14). Current clinical diagnostic and prognostic methods can not accurately distinguish this small group of early stage cancer with aggressive potential from the more common less-aggressive early stage tumors (15). 
         [0006]    Humphrey P A has given a comprehensive review of Gleason grading and current status of clinical methods in diagnosis and prognosis of prostate cancer (15-16). Today, the Partin Table is the most widely used method for choosing proper treatment (17-18) integrating important clinical parameters to predict the pathological stage. Important parameters are Gleason score of needle core biopsy, serum PSA level and clinical stage. Of all parameters, cytological grade or Gleason grading of biopsy samples is currently the key method for confirming the diagnosis of prostate cancer, and has demonstrated strong association with cancer specific survival. However, Gleason grading is not satisfactory for predicting cancer outcome when tumors are small, in particular when tumors are moderately differentiated with a biopsy Gleason score 6, the most common Gleason sum in clinical biopsy cases (15). Quite often, a diagnosis of prostate cancer is uncertain due to insufficient, or lack of, malignant structures, rendering further prediction of cancer outcome impossible (15). Waiting time for capturing confirmative malignant structure by repeated biopsy procedures may miss the right time window to cure patients with life-threatening cancer at very early stage. On the other hand, uncertain outcome prediction causes reduction of life quality in patients with virtually harmless cancer when they are treated with radical surgery. There is currently a strong need for a new diagnostic and prognostic method that can complement and improve Gleason grading system in three aspects (19): firstly, it should directly reflect biological aggressiveness, i.e. be able to predict different outcome of tumors with the same Gleason grade, in particular tumors with Gleason score 6; secondly, it should apply to small biopsy samples; thirdly, it should be able to predict tumor aggressiveness using biopsy samples from cancerous prostate with insufficient malignant structure, overcoming problems with small tumors and heterogeneous tumors that limit the accuracy of histopathological evaluation of biopsy samples. 
         [0007]    An abundance of experimental data shows that cancer is caused by genomic alterations. Weinberg R A and associates as well as Vogelstein S and associates reviewed these data and developed them into generally accepted theories of the molecular genetics and biology of cancer (20-26). Briefly, the genomic changes involved include DNA sequence changes, such as base change, deletion, copy number gain, amplification and translocation, as well as DNA modification such as promoter methylation. These genomic changes cause gene expression alterations that further cause biological alterations in the cell, such as accelerated cell cycle, alteration of cell-cell contact and signaling, increase of genomic instability, escape from apoptosis, increase of cell mobility, activation of angiogenesis and escape from immune surveillance. It has been shown that five to six genomic alterations are needed to establish a malignant phenotype of invasion and metastasis, meaning that multiple biological functional alterations are required. Different initial and subsequent key genomic events may determine different potential of invasion and metastasis, a basis for using molecular genetic markers to predict clinical outcome of cancer (20-26). So far, only a few genetic or epigenetic alterations have been identified in prostate cancer at individual gene level, such as germline mutations of RNASEL (HPC1) and ELAC2 (HPC2) in patients with hereditary prostate cancer, somatic mutations of PTEN, EPHB2 and AR in sporadic prostate cancer, and promoter methylation of GSTP1 in prostate cancer tissues (27-34). Nelson W G, De Mazo A and Isaacs W B have concisely reviewed the current status of prostate cancer molecular genetic and biological studies (11; 35-36). Tricoli J V and associates have summarized all putative diagnostic and prognostic markers of prostate cancer (19). An important question remains: no single molecular biomarker has turned out to be superior to the Gleason grading system. This is due to the fact that Gleason grading is a morphological profiling indirectly reflecting most important biological alterations, whereas a single biomarker may merely reflect alterations of one or two biological pathways in cancer cells. The broad spectrum of tumor genotype alterations and phenotype variations has hindered successful translation of findings from most single marker analysis into useful clinical markers for predicting disease outcome. 
         [0008]    In contrast, high throughput methods such as DNA arrays allow profiling of molecular signatures indicating alterations of multiple cellular processes (37). There is an increasing body of studies of using gene expression profiling to extract specific expression patterns or signatures attributed to different biological forms of cancer, and further using these gene expression features to predict clinical outcome of early stage cancer, e.g. breast cancer (5; 6). There are also several publications on gene expression profiling of human prostate cancer (1; 7; 38-54). Their quality differs by array complexity, number of cases and tissue samples studied, but they share two limitations: (i) they used a small number of cases selected by surgery with short time follow-up; (ii) antibody availability limited the use of immunohistochemistry to verify clinical importance of most new genes in a large series of tissue arrays. Proteins as markers do not always reflect RNA alterations. 
         [0009]    Despite these disadvantages, previous studies have identified several new markers that are potentially useful in clinics, such as AMACR in distinguishing cancer from non-cancer lesions, HPN, PIM1 and EZH2 in prognosis, as well as AZGP1 and MUC1 in distinguishing different forms of primary tumors. However, none of these markers is superior to Gleason grading. 
         [0010]    In earlier co-operative work with Stanford University the present inventor carried out gene expression profiling in a large set of normal prostate tissues, prostate tumors and lymph node metastases. Using various statistical approaches, a few hundreds genes were identified, the expression of which allows to distinguish low grade from high grade tumors, and even to predict the risk of short-term recurrence after radical surgery. High throughput tissue microarray analysis with a series of selected markers has found that MUC1 showed significant increased expression in tumors with poor prognosis and AZGP1 showed increased expression in tumors with good prognosis. However, even the two markers in combination do not have the same predictive power as histopathological evaluation using the Gleason grading system. This indicates the limitation of this marker lottery approach (1). 
         [0011]    Thus, with the advancement of biological and genetic research, knowledge about initiation and progression of cancer has greatly increased in recent time. Successful use of such knowledge in clinical diagnosis, prognosis and treatment for cancer patients, however, has been limited so far. 
         [0012]    A highly relevant problem is how to predict the outcome of a tumor in a patient. Predictive methods available today are based on the concept that all tumor cells in a specific tumor are of the same functional importance. New data has shown that the total tumor cell population can be divided into two populations, i.e., a small tumor stem cell population and a large partially differentiated tumor cell population. Tumor stem cells are malignant cells that can proliferate, invade and metastasize, whereas differentiated tumor cells do not possess these properties. 
         [0013]    Most conventional methods in this field rely on one or a few tumor markers only for diagnosis and prognosis. Tumor initiation and progression is however a complex biological process involving multiple genetic and functional changes in the tumor stem cells, which can not be simply reflected by one or a few tumor markers. Therefore using one or a few tumor markers to predict tumor outcome cannot reach a level of accuracy required by clinicians and patients for proper choice of treatment alternatives. On the other hand, the indiscriminate use of all tumor markers available in a prediction method results in high experimental and methodical complexity, and thus is time consuming and costly. It is this deficiency that the present invention seeks to remedy. 
       OBJECTS OF THE INVENTION 
       [0014]    It is an object of the invention to provide a method for predicting the development of cancer at an early stage of tumor development. 
         [0015]    It is another object of the invention to provide a method for identifying, in a group of persons diagnosed to have a cancer, a sub-group of persons in which the cancer should be treated. 
         [0016]    It is a further object of the invention to provide a method for assigning a suitable treatment to a person pertaining to a group of persons in which the cancer should be treated. 
         [0017]    Still further objects of the invention will become evident from the study of the following description of the invention and a number of preferred embodiments thereof, and of the appended claims. 
       SUMMARY OF THE INVENTION 
       [0018]    The present invention is based on the concept that a method for predicting the development of cancer should be based on the genetic profile of tumor stem cells, notwithstanding that they do comprise only a small portion of the total tumor cell population. 
         [0019]    Embryonic stem cell (ES) gene markers of the invention are herein referred to as ES tumor predictor genes (ESTP genes). The gene symbols for the ESTP genes of the invention are given according to their standard symbols in the National Center for Biotechnology Information&#39;s gene database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&amp;cmd=search&amp;term). For expressed sequence tag (EST) without gene symbol, the IMAGE clone ID or the UniGene cluster ID is given. 
         [0020]    The present invention is further based on the concept that embryonic stem cells are the origin of all tissue cells including so called progenitor cells of various specific cell lineages or cell types. Tumor cells may be derived from a few tissue stem cells whose regulatory system to guide time- and space-specific differentiation is disabled due to incorrectly repaired DNA damage. Despite impaired differentiation, other stem cell functional properties are more or less maintained or even enhanced, such as proliferation and metastasis. Thus, the more stem cell properties are conserved in the tumor cells, the more aggressive they will be biologically and clinically. 
         [0021]    Based on this hypothesis a series of published original datasets in the Stanford Microarray Database (SMD) was analyzed according to the present invention. The datasets are derived from gene expression profiling studies in embryonic cell lines and cancers of the prostate, breast, lung, brain, stomach, kidney, ovary and blood. The expression profile of ESTP genes, that is, genes strongly regulated in ES tumor cells, allows to predict histological as well as biological subtypes with different clinical outcomes. In this application, “strongly regulated” applies to ESTP genes with a specific high expression level but also to ESTP genes with a specific low expression level. 
         [0022]    Thus the present invention is additionally based on the hypothesis that strongly regulated ESTP genes in ES tumor cells, play a crucial role in tumor development and that, more specifically, different patterns of expression alterations of these ESTP genes determine tumor aggressiveness. According to the present invention this hypothesis is validated by using a large series of published datasets of genome-wide gene expression profiling in ES cells and in normal and tumor tissues for identifying ES genes of high prognostic power, that is, ESTP genes: 
         [0023]    By a simple one class ranking test method, a list of 641 genes was identified, of which 328 display with highest level of expression and 313 with lowest level of expression in ES tumor cells (p≦0.05). The gene expression data of these ESTP genes were derived from a variety of normal and tumor tissue samples, in total about 1000 tissue samples (arrays). They can be used to predict pathological and clinical characteristics of a tumor in a patient by applying a simple hierarchical cluster method to a corresponding dataset obtained for the respective tumor. By this method high prognostic accuracy was obtained for all tumor types investigated, in particular prostate cancer but also gastric cancer, lung cancer, and leukemia. Moreover, prognostic accuracy was also obtained for breast cancer, ovary cancer, brain tumor, soft tissue tumor, and kidney cander. 
         [0024]    Most important, according to the present invention, prognostic analysis is based on the genes with highest and lowest level of expression, that is, genes within ranges of expression which are near or comprise the level of maximal expression and of minimal expression. 
         [0025]    Identification of pathological and clinical tumor characteristics by the ES gene expression profile of a tumor according to the present invention is competitive with and may be even superior to that obtained by complex statistical methods known in the art using the original expression datasets in a complete genome-wide scale analysis comprising over 20,000 genes. The present invention provides a prognostic method of predicting tumor pathological and clinical characteristics in a patient based on a restricted number of ES genes, such as less than 2,500 ES genes, more preferred less than 1,000, even more preferred from 500 to 750 ES genes, in particular from 600 to 680 ES genes, most preferred about 641 ES genes. The relatively small number of ES genes used for prediction, such as about 641 ES genes, and their specific functionality in stem cell biology allows errors due to biological and methodological background noise to be reduced or even eliminated. Virtual experimental methods based on such a restricted number of ES genes can be used for the diagnosis and prognosis of a broad spectrum of tumors. In contrast methods known in the art usually rely on few markers restricted to different tumor types. Based on the ESTP genes of the invention, a variety of robust analytical methods can be designed and applied in tumor diagnosis and prognosis using trace amounts of RNA derived from small tumor samples. For most tumors, such as prostate cancer, there is no method known in the art capable of predicting with good accuracy clinical outcome at an early stage of tumor development. It is in particular here that the prognostic method of the invention solves an important clinical problem. 
         [0026]    In the following are disclosed preferred aspects of limiting the number of ESTP genes on which the method of the invention is based.
       (I) A first preferred aspect comprises selecting ES genes of predictive significance, that is, ESTP genes that constitute a minor proportion of all ES genes, in a cancer;   (II) According to a second preferred other statistical methods can be applied to derive substantially similar ES genes for the prediction of tumor pathological and clinical characteristics as described above;   (III) According to a third preferred aspect of the invention genes with weak prediction power are eliminated from the list of ES genes identified by the method of the invention and thus from consideration, thereby reducing the number of ESTP genes and improving prediction accuracy;   (IV) According to a fourth preferred aspect of the invention a number of ESTP genes with high specificity are selected from the ES gene list obtained by the method of the invention for application to a specific type of tumor, such as prostate cancer or breast cancer;   (V) According to a fifth preferred aspect of the invention methods known in the art used in diagnosis and prognosis of tumors are based on one or several ESTP genes identified by the method of the invention, such as multiplex or high throughput RT-PCR (reverse transcriptase polymerase chain reaction) using small amounts of tumor samples, a specific DNA microarray platform, and other low or high throughput RNA analytical methods.       
 
         [0032]    FNA (Fine Needle Aspiration) biopsy for clinical diagnosis and prognosis allows sampling multiple areas to cover a large volume of a tumor due to its minimal morbidity, thus being superior in overcoming tumor heterogeneity. Once the needle is inserted into a tumor lesion, it allows to obtain very pure cytological aspirates from the tumor with minimal stromal or normal epithelial cell contamination. FNA biopsy is a preferred method for obtaining pure tumor samples for molecular diagnosis and prognosis from small tumors, in particular from early stage prostate tumors. Conventional cDNA array experiments require approximately 40 μg total RNA. FNA biopsy yields 100-2,000 ng total RNA (57-59). This small amount of RNA is sufficient for analyses by using a small array platform as well as by multiplex or other high throughput RT-PCR methods. 
         [0033]    Thus, according to the present invention is disclosed a method of predicting the development of a cancer in a patient, comprising:
       (i) procuring a sample of tumour tissue from the patient;   (ii) determining the expression pattern of embryonic stem cell genes in the tissue;   (iii) comparing said expression pattern with the corresponding expression pattern of embryonic stem cell genes in tumour tissue of reference patients with known disease histories.       
 
         [0037]    According to the present invention is disclosed, in particular, a method of predicting the development of a cancer in a patient, comprising:
       (a) procuring a tumour tissue from the patient;   (b) determining an expression pattern of embryonic stem cell genes listed in Table 1;   (c) comparing said expression pattern with a corresponding expression pattern of embryonic stem cell genes in tumour tissue of reference patients with known disease histories;   (d) identifying the patient or patients with known disease histories whose expression pattern optimally matches the patient&#39;s expression pattern;   (e) assigning, in a prospective manner, the disease history of said patient(s) to the patient in which the development of cancer shall be predicted.       
 
         [0043]    It is preferred for the determination of the expression pattern of said embryonic stem cell genes to comprise that of a first group genes with high level of expression and that of a group of genes with a low level of expression, said first and second group of genes not comprising by a third group of genes with intermediate levels of expression. 
         [0044]    It is particularly preferred for the genes in the first group and/or the second group to be consecutive, that is, ranked consecutively, in respect of their expression levels. 
         [0045]    According to a preferred aspect of the invention it is preferred for the total number of genes in the first and second groups to be substantially smaller than the number of the genes in the third group, in particular less than a fifth of the number of the genes in the third group. The total number of genes in the first and second groups is preferably from 500 to 750, more preferred from 600 to 680, most preferred about 641. 
         [0046]    The genes pertaining to the first and second groups are preferably identified by employing a q value of from 0.01 to 0.1, more preferred of from 0.025 to 0.075, most preferred of about 0.05, in a one class significant analysis of microarrays (SAM) on a centered embryonic stem cell gene dataset by which all genes are ranked according to their expression levels 
         [0047]    The method of the invention is applicable to cancer of any kind, in particular to prostate cancer, gastric cancer, lung cancer, and leukemia. 
         [0048]    According to a second preferred aspect of the invention is disclosed the use of an embryonic stem cell gene DNA or RNA microarray for predicting the development of a cancer tumor in a patient. Preferably the microarray comprises DNA or RNA of a first group of embryonic stem cell genes with high level of expression in the tumor and of a second group of embryonic stem cell genes with a low level of expression in the tumor but not comprising DNA or RNA, respectively, of embryonic stem cell genes with an intermediate level of expression in the tumor. It is also preferred for the genes in the first and second groups to be those ranked according to their expression levels, in particular in a consecutive manner. A preferred method of ranking is a one class significant analysis of microarrays (SAM) on a centered embryonic tumor stem cell gene dataset by employing a q value of from 0.01 to 0.1, more preferred of from 0.025 to 0.075, most preferred of about 0.05. The embryonic stem cell gene DNA or RNA microarray can be used for the predictions of the development of any cancer, in particular of prostate cancer, gastric cancer, lung cancer, and leukemia and, furthermore, of breast cancer, ovary cancer, brain tumor, soft tissue tumor, and kidney tumour. 
         [0049]    According to a third preferred aspect of the invention is disclosed a microarray comprising a fragment of embryonic stem cell gene DNA or RNA derived from a first group of embryonic stem cell genes with high level of expression in a cancer tumor and from a second group of embryonic stem cell genes with a low level of expression in said cancer tumor but not comprising a fragment of embryonic stem cell gene DNA/RNA with an intermediate level of expression in the tumor. It is particularly preferred for the genes in the first group and/or the second group to be ranked consecutively in respect of their expression levels. It is preferred for the genes in the first and second groups to be those ranked according to their expression levels by a one class significant analysis of microarrays (SAM) on a centered embryonic tumor stem cell gene dataset by employing a q value of from 0.01 to 0.1, more preferred of from 0.025 to 0.075, most preferred of about 0.05. The cancer can be any cancer, in particular prostate cancer, gastric cancer, lung cancer, and leukemia but also breast cancer, ovary cancer, brain tumor, soft tissue tumour, and kidney tumor. 
         [0050]    According to a fourth preferred aspect of the invention is disclosed a probe comprising any of DNA, DNA fragment, DNA oligomer, DNA primer, RNA, RNA fragment, RNA oligomer of a first group of embryonic stem cell genes with high level of expression in a cancer tumor and of a second group of embryonic stem cell genes with a low level of expression in said cancer tumor but not comprising DNA, DNA fragment, DNA oligomer, DNA primer, RNA, RNA fragment, RNA oligomer, respectively, of embryonic stem cell genes with an intermediate level of expression in said cancer tumor. It is preferred for the genes in the first and second groups to be those ranked, preferably consecutively, according to their expression levels by a one class significant analysis of microarrays (SAM) on a centered embryonic tumor stem cell gene dataset by employing a q value of from 0.01 to 0.1, more preferred of from 0.025 to 0.075, most preferred of about 0.05. The cancer can be any cancer, in particular prostate cancer, gastric cancer, lung cancer, and leukemia but also breast cancer, ovary cancer, brain tumor, soft tissue tumor, and kidney cancer. 
         [0051]    According to a fifth preferred aspect of the invention is disclosed the use of a multitude of embryonic stem cell genes in a method of assessing the prognosis of a cancer tumor, wherein said multitude comprises a first group of embryonic stem cell genes with high level of expression in the tumor and of a second group of embryonic stem cell genes with a low level of expression in the tumor but does not comprise embryonic stem cell genes with an intermediate level of expression. It is preferred for the genes in the first and second groups to be ranked consecutively according to their expression levels and to constitute a fraction of the embryonic stem cell genes expressed in the tumor, in particular a fraction of 20 per cent or less of the embryonic stem cell genes expressed in the tumor. It is furthermore preferred to identify the multitude by a one class significant analysis of microarrays (SAM) on a centered embryonic tumor stem cell gene dataset by employing a q value of from 0.01 to 0.1, more preferred of from 0.025 to 0.075, most preferred of about 0.05. The use relates to any type of cancer, preferably prostate cancer, gastric cancer, lung cancer, and leukemia but also breast cancer, ovary cancer, brain tumor, soft tissue tumor, and kidney cancer. 
         [0052]    According to a sixth preferred aspect of the invention the ESTP genes in the first group and the second group can be for analysis of clinical tumor tissue biopsies or tumor cell aspirate samples using high throughput DNA microarrays for clinical diagnosis and prognosis. 
         [0053]    In a first preferred use is designed a gene microarray for probing the 641 or, less preferred, the aforementioned 1,000 or from 500 to 750 or, in particular, from 600 to 680 ESTP genes by spotting a DNA fragment (PCR products or oligos) of each of them on a glass or other suitable support. RNA isolated from tumor tissue biopsies or tumor cell aspirates can be labelled and hybridized with the ESTP gene microarray. The expression changes of all the 641 ES genes can be determined and compared with a group of standard reference cases with well defined data of clinical parameters such as histology, pathology and outcomes. The clinical outcomes of the new cases can thus be predicted. 
         [0054]    A second preferred use relies on a gene solution array, for instance one based on the xMAP technology (http://www.luminexcorp.com). Probes that specifically bind to RNA of the ESTP genes can be designed, synthesized and immobilized on the surface of a microsphere or microbead support. RNA isolated from clinical tumor tissue biopsies or tumor cell aspirates can be bound to the support. Upon illuminating the beads/spheres with light of varying wavelength under laser beam activation the expression levels of the various ESTP genes in the tumor samples can be simultaneously and accurately measured. This method is simple, sensitive, and accurate and of high throughput; the expression levels of up to 100 genes can be in one experiment. 
         [0055]    A third preferred use comprises the design of probes for assembling an ESTP gene microarray or chip of any kinds, for the purpose of application in clinical diagnosis and prognosis of common cancers. 
         [0056]    According to a seventh preferred aspect of the invention high throughput PT-PCR can be used for analysis of clinical tumor tissue biopsies or tumor cell aspirate samples. Based on the ESTP gene list, design primers for each gene can be designed to carry out multiplex RT-PCR for determining the expression level of each gene in a tumor tissue or aspirate sample. Since the common RT-PCR platform can analyze 96 or multiple sets of 96 samples simultaneously, a small number of multiplex RT-PCR suffice to achieve high throughput measurement of the expression levels of the most preferred 641 ESTP genes or the less preferred 1000 or from 500 to 750 or, in particular, from 600 to 680 ESTP genes in a large set of clinical tumor tissue biopsies or aspirates. 
         [0057]    According to an eight preferred aspect of the invention clinical tumor tissue biopsy samples and tumor cell aspirate samples can be analyzed using high throughput protein/antibody microarrays or an ELISA method. Based on the most preferred 641 ESTP genes or the less preferred 1000 or from 500 to 750 or, in particular, from 600 to 680 ESTP genes, the protein sequence or a portion thereof can be retrieved from publicly available human genome sequence resources and used to produce specific monoclonal antibodies for targeting the proteins encoded by the respective ESTP genes. The specific antibodies can be assembled into an ES protein array or incorporated into a high throughput ELISA system to measure the protein expression levels of the most preferred 641 ESTP genes and the less preferred 1000 or from 500 to 750 or, in particular, from 600 to 680 ESTP genes in clinical tumor tissue biopsies and tumor cell aspirates. 
         [0058]    The invention will now be explained in greater detail by reference to preferred embodiments illustrated in a drawing. 
     
    
     
       DESCRIPTION OF THE FIGURES 
         [0059]      FIG. 1  is a graph illustrating the identification of ES predictor genes by a one-class SAM ranking test; 
           [0060]      FIG. 2  is a gene expression profile obtained from biopsies of healthy and cancerous prostate tissue, and from embryonic stem cell lines, with a hierarchial clustering of the biopsies; 
           [0061]      FIG. 3  is a gene expression profile obtained from biopsies of healthy and cancerous lung tissue biopsies, and from embryonic stem cell lines, with a hierarchial clustering of the biopsies; 
           [0062]      FIG. 4  is a graph illustrating survival for the patients related to major cancerous lung tissue clusters of  FIG. 3 ; 
           [0063]      FIG. 5  is a gene expression profile obtained from biopsies of healthy and cancerous stomach tissue biopsies, and from embryonic stem cell lines, with a hierarchial clustering of the biopsies; 
           [0064]      FIG. 6  is a graph illustrating survival for the patients related to major cancerous gastric tissue clusters of  FIG. 5 ; 
           [0065]      FIG. 7  is a gene expression profile obtained from leukocytes of acute myeloid leukemia patients, and from embryonic stem cell lines, with a hierarchial clustering of the leukocyte samples; 
           [0066]      FIG. 8  is a graph illustrating survival for the patients pertaining to the major acute myeloid leukemia subtype clusters of  FIG. 7 . 
       
    
    
     DESCRIPTION OF PREFERRED EMBODIMENTS 
     Example 1 
       [0067]    Data Retrieval. The method of the invention is based on published gene data such as the data sets published and deposited in the Stanford Microarray Database (SMD) (http://genome-www5.stanford.edu/). All array experiments used the same two-dye cDNA array platform with a common RNA reference, which enables reliable combination of or comparison with data from different experiments. These datasets include genome-wide expression data for embryonic stem cells (60), normal tissues from most of the human organs (61), and tumors from the prostate (62), breast, lung (63), stomach (64), liver (65), blood (66), brain (67), kidney (68), soft tissue (69), ovary (70; 71) and pancreas (72). In total about 1000 arrays were included in the analysis. Each array (tissue) in these datasets is denoted with corresponding basic clinical and pathological information such as histopathological type, tumor grade, clinical stage, and even survival data in a significant fraction of tumor cases. 
         [0068]    Gene Selection. All genes or clones on arrays are selected. Control spots and empty spots are not included. 
         [0069]    Data Collapse/Retrieval. Raw data are retrieved and averaged by SUID; UID column contains NAME; Retrieved Log(base2) of R/G Normalized Ratio (Mean). Data filtering options: Selected Data Filters: Spot is not flagged by experimenter. Data filters for GENEPIX result sets: Channel 1 Mean Intensity/Median Background Intensity&gt;1.5 AND Channel 2 Normalized (Mean Intensity/Median Background Intensity)&gt;1.5. 
         [0070]    Data centering. The ES cell data set was combined with each of a number of other data sets. Genes and array batches were centered separately in each combined dataset as previously described (61; 62). 
       Example 2 
       [0071]    Identification of ES predictor genes. After centering a data set containing ES cells and normal tissues from most human organs, the ES data set was separated from the normal tissue data set. A one-class SAM (significant analysis of microarrays) was carried out using the centered ES dataset, by which all genes were ranked according to their expression levels in the ES cells (73). Using a q value equal to or less than 0.05 as cut-off, top 328 genes with highest level and top 313 genes with lowest level of expression in the ES cells were identified (Table 1). These 641 ES genes are named ES tumor predictor genes (ESTP genes). Previous studies used a small number of sample matrices to normalize the expression data of ES cells (60; 74); this may lead to erroneous identification of ESTP genes. In this invention, the expression data of ES genes from ES cells were centered by a matrix of over 100 normal tissues from most human organs (62). This greatly reduced erroneous identification of ESTP genes. 
       Example 3 
       [0072]    Prediction of clinical and pathological tumor types. After centering each combined data set, a sub-dataset containing only the 641 ESTP genes was isolated from the original dataset. A simple hierarchical clustering was carried out based on this sub-dataset using genes with 70% qualified data in all samples (78). The sample grouping was directly correlated with the clinical and pathological information of each individual tissue sample. Prediction examples for a number of tumor types are given below. Prediction in other datasets is carried out in essentially the same manner. 
         [0073]    In the one class SAM analysis, numbers of genes selected is in correlation with q value. There were 201 genes selected when q value at 0.01, 641 genes selected when q value at 0.05, and 1368 genes selected when q value at 0.1. In other words, an increased q value would result in increased number of selected genes as well as increased number of genes that would not be associated with the transcriptional regulation in the ES cells. 
         [0074]    Importantly, when the prediction powers were compared, the 641 genes selected by q value at 0.05 had best classification (prediction) results, as shown in the prostate cancer (Table 2) and lung cancer (Table 3) materials. The difference was particularly obvious in respect of lung cancer (Table 3). Thus the 641 genes selected by q value at 0.05 was the best choice of gene selection when both stem cell association and tumor classification are taken into consideration. 
         [0075]    Definition of prediction. As described above, the ESTP genes were derived from the ES cell dataset. The power of this set of genes in the classification of a broad spectrum of tumors was then validated in each independent tumor dataset. 
       Example 4 
       [0076]    Prostate cancer. Published clinical data and predicted tumor subtype by ESTP genes of the invention for prostate cancer are listed in Table 2: Gleason grade, stage, biological subtype and short term recurrence (prostate specific antigen (PSA) survival) after radical surgery. Of the 641 ESTP genes, 505 had good data in 70% of all samples. In the gene expression profile of  FIG. 2 , the expression level (range in log ratio between −5.06 and 6.15) was transformed into a transitional color presentation, with red indicating above 0, black equal to 0 and green for less than 0; in  FIG. 2  and the other figures illustrating gene expression profiles the colors are rendered in white, black, and grey (see, DESCRIPTION OF THE FIGURES). Based on these expression data, all samples were classified by hierarchical clustering into distinct groups as normal prostate, embryonic stem (ES) cells, prostate cancer group that contained all cases (66) with recurrence (PCa recurrent), Prostate cancer group that contained only cases without recurrence (PCa non-recurrent), and ES carcinoma cells. The classification is significantly (Fisher&#39;s exact test, p=0.001) correlated with the previous classification by using 5000 genes (Lapointe J et al., 2004). It should be noted that the PCa non-recurrent group predicted by the present invention is also significantly correlated with low Gleason score&lt;6 (Fisher&#39;s exact test, p=0.028) and early stage (T&lt;T3) (Fisher&#39;s exact test, p=0.007). 
         [0077]    Prediction value for choice of treatment. Patients with a tumor predicted to be of a recurrent type (pertaining to the recurrent group) should be treated by radical surgery at a very early stage even in case of a moderate or low Gleason score. Patients with a very early stage tumor predicted to be of a non-recurrent type (pertaining to the non-recurrent group) should be kept under regular PSA and other examination control, because most of the tumors in this group are in fact indolent or very slow-progressive. 
       Example 5 
       [0078]    Lung cancer. Published clinical data and predicted tumor subtype by ESTP genes of the invention are shown in Table 3. Prediction of histological type and survival in lung cancer is illustrated in  FIG. 3 , tissue clustering by ESTP genes. Of the 641 ES predictor genes, 316 had qualified data in 70% or more of the samples. Lung cancer tissue samples were predictively sorted into two major groups, an adenocarcinoma group (a) that mainly contained adenocarcinomas, some normal lung tissues, ES cells and a few non-adenocarcinomas, and a (b) non-adenocarcinoma group that contained most non-adenocarcinomas including squamous cell carcinoma, large cell lung cancer and small cell lung cancer, together with a fraction of adenocarcinomas. In general, adenocarcinoma has a better prognosis than other types of lung cancer. Survival analysis based on lung adenocarcinoma subtypes is illustrated in  FIG. 4 . 
         [0079]    The adenocarcinoma cases in the non-adenocarcinoma group (b) further showed shorter survival than adenocarcinoma cases in the adenocarcinoma group (a) as shown in  FIG. 3 , adenocarcinoma subtypes by ES predictor genes associated with survival. 
         [0080]    Predictive value for choice of treatment strategy: tumors predicted to pertain to the adenocarcinoma group seem to have a generally favorable outcome after radical surgery at a very early stage; whereas tumors in the non-adenocarcinoma group may respond relatively better to chemotherapy such as to Iressa or radiation. 
       Example 6 
       [0081]    Gastric cancer. Published clinical data and tumor subtype predicted by ESTP genes of the invention are illustrated in Table 4. The prediction of histological types and survival in gastric cancer is illustrated in  FIG. 5 : (a) tissue clustering by ES predictor genes; (b) issue subtypes by ES predictor genes associated with survival. 
         [0082]    Prediction of subtypes of gastric cancer by ESTP genes: of the 641 ESTP genes 613 had qualified data in 70% of all samples. Gastric tumors were classified into two major subtypes, type 1 enriched in tumors with diffuse and mix histological types generally with poor prognosis, type 0 together with most normal gastric tissue samples. The survival time for gastric cancer patients pertaining to these groups is compared in  FIG. 6 . The subtype 0 tumors can be further divided into two sub-subtypes, one with the A subtype enriched in EB virus positive tumors, the other not. 
         [0083]    Predictive value: a) EBV infection is linked to gastric cancer via stem cell biology. Preventing an EBV infection by vaccination may have preventive effect on gastric cancer; b) Diffused type of gastric cancer has very strong hereditary tendency. One should specifically exclude gastric cancer in a relative to a patient whose tumor is predicted to pertain to this group, so that possible tumor can be treated radically at a very early stage. 
       Example 7 
       [0084]    Leukemia. Published clinical data and predicted tumor subtype by ESTP genes of the invention are listed in Table 5.  FIG. 7  illustrates the prediction of subtypes of acute mononucleocyte leukemia associated with chromosome aberration and survival: (a) classification by ESTP genes; (b) AML subtypes associated with survival. Prediction of acute myeloid leukemia (AML) by ESTP genes: of the 641 ES predictor genes, 324 had qualified data in 70% of all samples. AML cases were classified into two major subtypes, type 1 enriched in cases with t(8;21) and del7q chromosomal aberrations, and type 0, which was further divided into two sub-subtypes A and B the first with a subtype enriched with inv(16), the second enriched with t(15;17). Type 1 cases showed shorter overall survival than type 0 as presented in  FIG. 8 . Survival analysis was based on AML subtypes predicted in  FIG. 4   a  and the published clinical data in Table 5. 
         [0085]    Predictive value for treatment choices: AML with different chromosomal aberrations responds to different chemotherapies; in particular all-trans retinoic acid can induce differentiation of AML with t(15;17) translocation. It is suggested that AML in the group enriched with t(15;17) but without the translocation detected by cytogenetic diagnostic method may show good response to all-trans retinoic acid due to the same stem cell biological alteration. 
       Example 8 
       [0086]    Case History and Retrospective Cancer Treatment Strategy Suggested by the Method of the Invention. 
         [0087]    (a) Prostate cancer patient #PC007 (Table 5) aged 56 y at diagnosis. Gleason score of prostate cancer was 3+3=6; tumor stage was T2b, suggesting a well differentiated tumor at an early stage by conventional clinical pathological examination. In spite of this the tumor recurred as diagnosed by a re-increased PSA level 27.7 months after radical surgery. According to the predictive method of the invention, the tumor is predicted to be of ES type 1 with poor prognosis. This case illustrates a typical situation in which ES type prediction can outperform conventional clinical pathological methods in predicting clinical outcome. A similar case is patient PC250 (Table 5). 
         [0088]    (b) Prostate cancer patient #PC037 (Table 5). This 57 year-old patient had a Gleason 4+3 tumor, a high grade tumor that would have a poor prognosis according to conventional clinical concepts. But, according to the predictive method of the invention, the tumor is classified as being of ES type 0 and thus would have had a better prognosis. The patient had a radical surgery without any signs of recurrence after 16.2 months. This case provides also an example for the situation that the ES typing in the present invention is superior to conventional Gleason grading. 
         [0089]    (c) Prostate cancer patient #PC092 (Table 5). This patient was aged 68 y at diagnosis. His tumor had Gleason 3+3=6 and staged T2b, suggesting a well differentiated tumor at an early stage. By the method of the present invention the tumor is classified as being of ES type 0 with good prognosis. The patient was treated by radical surgery. No signs of recurrence were observed 13.7 months post surgery. There is good agreement between Gleason grading and ES typing according to the present invention. The ES typing result also suggests that the patient could have been safely kept under regular PSA control instead of immediate radical surgery. 
       Example 9 
       [0090]    Prognosis of lung adenocarcinoma. In addition to the prostate cancer cases from Table 5 elucidated above, it is seen that ES typing according to the present invention is significantly better than conventional histological grading in the prognosis of lung adenocarcinoma. For example, cases #222-97 and #226-97 were of grade 3 that would be poorly differentiated with poor outcome according to conventional clinical prognostic methods. By the method of the present invention the cases are classified as being of ES type 0 that would have a relatively good outcome. The patients were recurrence-free more than 48 months after radical surgery. Again ES typing by the method of the invention is more accurate than by conventional histological grading. 
       Legends to Figures 
       [0091]      FIG. 1 . Identification of ESTP genes by a one-class SAM ranking test. There were 24361 genes with qualified expression data in 75% of the 6 embryonic stem (ES) cell lines. These 24361 genes were ranked according to their homogenous expression levels in the ES cells by a one-class SAM (significant analysis of microarrays) method as shown in this figure. At delta 0.23, q value&lt;0.05, 328 genes with highest expression levels and 313 genes with lowest expression levels were identified. The expression changes of these 641 genes in different tumor samples showed also strongest classification power as compared to genes located within the cut-off lines. Increasing the delta value (decreasing the q value) can increase the specificity in selecting genes representing the transcriptional regulation in the ES cells whereas it can decrease the number of selected genes. A decrease in significant genes selected could result in a decrease in the corresponding tumor classification power. By successively changing the cut-off line it was shown that the 641 genes selected at delta 0.23, q value&lt;0.05 was the best choice for both stem cell association and tumor classification. 
         [0092]      FIG. 2 . Prediction of prostate cancer—Gleason grade, stage, biological subtype and short term recurrence (prostate specific antigen (PSA) survival) after radical surgery. Of the 641 ESTP genes, 505 had good data in 70% of all samples. In this gene expression profile, the expression level (range in log ratio between −5.06 and 6.15) was transformed into a transitional gray-black scale presentation, with black indicating above 1, median gray indicate equal to 1 and green for less than 1. Based on these expression data, all samples were classified by hierarchical clustering into distinct groups as normal prostate, prostate cancer aggressive group type 1 that contained all cases with recurrence, prostate cancer non-aggressive group type 0 that contained only cases without recurrence. The classification significantly (Fisher&#39;s exact test, p=0.001) correlated with the previous classification by using 5000 genes (Lapointe J et al., 2004). The non-aggressive group predicted by the present invention was also significantly correlated with low Gleason score &lt;6 (Fisher&#39;s exact test, p=0.028) and early stage (T&lt;T3) (Fisher&#39;s exact test, p=0.007). 
         [0093]    One tumor sample was provided for each prostate cancer patient. For some prostate cancer patients also a healthy (“normal”) tissue sample was provided from an unaffected prostate area. These normal samples formed the “normal” cluster in  FIG. 1 . There were 6 embryonic stem (ES) cell lines from non-prostate cancer subjects. In addition 10 embryonic carcinoma (EC) cell lines from patients with embryonic carcinoma were included. These ES and EC cell lines were used as reference to illustrate different patterns of gene expression. Importance of this prediction for treatment choices: patients whose tumor is predicted in the aggressive group type 1 should be treated by radical surgery at very early stage even if the tumor Gleason score is not high; whereas patients whose tumor is predicted in the non-aggressive group type 0 should be under regular PSA and other examination control if the tumor is at very early stage, because most of the tumors in this group are in fact indolent or progress very slowly. 
         [0094]      FIG. 3 . Prediction of lung cancer tissue type. Of the 641 ESTP genes, 316 had qualified data in 70% or more of the samples. Lung cancer tissue samples were predicted into two major groups, adenocarcinoma group type 0 that mainly contained adenocarcinomas, some normal lung tissues, ES cells and a few non-adenocarcinomas, and non-adenocarcinoma group type 1 that contained most non-adenocarcinomas including squamous cell carcinoma, large cell lung cancer and small cell lung cancer, together with a fraction of adenocarcinomas. In general, adenocarcinoma has relatively better prognosis than other types of lung cancer. In this invention, the adenocarcinoma cases in the non-adenocarcinoma group type 1 further showed shorter survival than adenocarcinoma cases in the adenocarcinoma group type 0 as shown in  FIG. 4 . 
         [0095]    All lung cancer patients had a tumor sample. A few patients had also a normal sample from the unaffected lung areas. These a few normal samples clustered together as shown in this figure. There were 6 embryonic stem (ES) cell lines from non-prostate cancer subjects. In addition 10 embryonic carcinoma (EC) cell lines from patients with embryonic carcinoma were also included. These ES and EC cell lines were used as reference to indicate different patterns of gene expression. 
         [0096]    Importance of the prediction for treatment strategy: tumors predicted in the adenocarcinoma group may have favourable outcome after radical surgery at very early stage. 
         [0097]      FIG. 4 . Lund adenocarcinoma survival analysis. The analysis is based on lung adenocarcinoma subtypes predicted in  FIG. 3  and the published clinical data reproduced in Table 3. Time unit: months. 
         [0098]      FIG. 5 . Prediction of subtypes of gastric cancer by ESTP genes. Of the 641 ESTP genes, 613 had qualified measuring in 70% of all samples. Gastric tumors were classified into two major subtypes, type 1 enriched with diffuse type and mix type tumors generally with poor prognosis, type 0 together with most normal gastric tissue samples. Type 0 tumors was further divided into two subtypes with the a subtype enriched with tumors with EB virus-positive. 
         [0099]    One tumor sample was provided from each gastric cancer patient. From some of the patients also a normal sample was taken from an unaffected stomach area. These “normal” samples formed the normal cluster in  FIG. 5 . There were 6 embryonic stem (ES) cell lines from non-prostate cancer subjects. In addition 10 embryonic carcinoma (EC) cell lines from patients with embryonic carcinoma were also included. These ES and EC cell lines were used as reference to indicate different patterns of gene expression. 
         [0100]    Importance of the prediction: a) EBV infection is linked to gastric cancer via stem cell biology. Preventing EBV infection by vaccination may have preventing effect on gastric cancer; b) diffused type of gastric cancer has a very strong hereditary tendency. One should specifically exclude gastric cancer in a relative to a patient, whose tumor is predicted in this group, so that a tumor, if detected, can be treated radically at very early stage. 
         [0101]      FIG. 6 . Gastric cancer survival analysis. The analysis was based on gastric cancer subtypes predicted in  FIG. 5  and on the published clinical data reproduced in Table 4. Time unit: months. 
         [0102]      FIG. 7 . Prediction of acute myeloid leukemia (AML) by ESTP genes. Of the 641 ES predictor genes, 324 had qualified data in 70% of all samples. AML cases were classified into two major subtypes, type 1 enriched in cases with t(8;21) and del7q chromosomal aberrations, type 0 that was further divided into two subtypes a and b with a subtype enriched inv(16) and b subtype enriched with t(15;17). Type 1 cases showed shorter overall survival than type 0 as presented in  FIG. 5 . 
         [0103]    From each patient one leukocyte sample was harvested. There were 6 embryonic stem (ES) cell lines from non-prostate cancer subjects. In addition 10 embryonic carcinoma (EC) cell lines from patients with embryonic carcinoma were also included. These ES and EC cell lines were used as reference to indicate different patterns of gene expression. 
         [0104]    Importance of the prediction for treatment choices: AML with different chromosomal aberrations respond to different chemotherapies, in particular all-trans retinoic acid can induce differentiation of AML with t(15;17) translocation. It is highly possible that AML in the group enriched with t(15;17) but without the translocation detected by cytogenetic diagnostic method can show good response to all-trans retinoic acid due to the same stem cell biological alteration. 
         [0105]      FIG. 8 . Leukemia survival analysis. The analysis was based on AML subtypes predicted in  FIG. 7  and on the published clinical data reproduced in Table 5. Time unit: months. 
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                 TABLE 1 
               
             
             
               
                   
               
               
                 Genes with extreme (highest and lowest) expression levels in ES cells 
               
             
          
           
               
                 Strongly positive expression level score (d) 
                 Strongly negative expression level score (d) 
               
               
                 (continued on the left of the following pages) 
                 (continued on the right of the following pages) 
               
             
          
           
               
                 IMAGE 
                 Gene 
                   
                 q-Value × 
                 IMAGE 
                 Gene 
                   
                 q-Value × 
               
               
                 clone 
                 symbol 
                 Score (d) 
                 10 2   
                 clone 
                 symbol 
                 Score (d) 
                 10 2   
               
               
                   
               
             
          
           
               
                 840944 
                 EGR1 
                 2.00 
                 0.67 
                 490023 
                 WNT5B 
                 −1.61 
                 0.67 
               
               
                 753104 
                 DCT 
                 1.95 
                 0.67 
                 433257 
                 LOC285458 
                 −1.49 
                 0.67 
               
               
                 1680098 
                 Hs.545599 
                 1.79 
                 0.67 
                 1628121 
                 ABCG2 
                 −1.43 
                 0.67 
               
               
                 1944026 
                 TAGLN 
                 1.74 
                 0.67 
                 781289 
                 AA429944 
                 −1.41 
                 0.67 
               
               
                 898092 
                 CTGF 
                 1.74 
                 0.67 
                 796542 
                 ETV5 
                 −1.39 
                 0.67 
               
               
                 526657 
                 TCEB3 
                 1.70 
                 0.67 
                 1948085 
                 GBR3 
                 −1.30 
                 0.67 
               
               
                 526184 
                 Hs.551490 
                 1.67 
                 0.67 
                 2017535 
                 LRP4 
                 −1.29 
                 0.67 
               
               
                 384111 
                 AA702568 
                 1.57 
                 0.67 
                 1556056 
                 PRPH 
                 −1.29 
                 0.67 
               
               
                 452134 
                 AA707225 
                 1.51 
                 0.67 
                 462144 
                 ARSE 
                 −1.29 
                 0.67 
               
               
                 360254 
                 CYR61 
                 1.49 
                 0.67 
                 415619 
                 SLC5A9 
                 −1.28 
                 0.67 
               
               
                 80186 
                 Hs.534427 
                 1.49 
                 0.67 
                 1389018 
                 CA4 
                 −1.27 
                 0.67 
               
               
                 301068 
                 Hs.433075 
                 1.44 
                 0.67 
                 143966 
                 SEPT6 
                 −1.25 
                 0.67 
               
               
                 1607286 
                 CYR61 
                 1.42 
                 0.67 
                 502151 
                 SLC16A3 
                 −1.24 
                 0.67 
               
               
                 378488 
                 CYR61 
                 1.42 
                 0.67 
                 1519951 
                 ETV5 
                 −1.22 
                 0.67 
               
               
                 306841 
                 Hs.419777 
                 1.37 
                 0.67 
                 450938 
                 DKFZP586A0522 
                 −1.22 
                 0.67 
               
               
                 53245 
                 LOC150383 
                 1.35 
                 0.67 
                 1323448 
                 CRIP1 
                 −1.19 
                 0.67 
               
               
                 1660645 
                 CYP26A1 
                 1.32 
                 0.67 
                 324593 
                 MGC16291 
                 −1.17 
                 0.67 
               
               
                 33837 
                 FRAS1 
                 1.29 
                 0.67 
                 824933 
                 NF1 
                 −1.16 
                 0.67 
               
               
                 2012523 
                 STX3A 
                 1.27 
                 0.67 
                 1742419 
                 WNT11 
                 −1.10 
                 0.67 
               
               
                 38642 
                 CYP26A1 
                 1.26 
                 0.67 
                 70152 
                 DKFZP586A0522 
                 −1.09 
                 0.67 
               
               
                 1473274 
                 MYL9 
                 1.23 
                 0.67 
                 1613496 
                 Hs.505172 
                 −1.08 
                 0.67 
               
               
                 1434897 
                 COL5A2 
                 1.22 
                 0.67 
                 461488 
                 ARRB1 
                 −1.08 
                 0.67 
               
               
                 307244 
                 LIPL3 
                 1.22 
                 0.67 
                 783697 
                 AA446838 
                 −1.07 
                 0.67 
               
               
                 1567658 
                 AA976207 
                 1.21 
                 0.67 
                 22355 
                 RGS4 
                 −1.07 
                 0.67 
               
               
                 49707 
                 Hs.517502 
                 1.20 
                 0.67 
                 913672 
                 Hs.430369 
                 −1.07 
                 0.67 
               
               
                 950676 
                 KIF1A 
                 1.17 
                 0.67 
                 1521792 
                 IBRDC3 
                 −1.07 
                 0.67 
               
               
                 843098 
                 BASP1 
                 1.17 
                 0.67 
                 51672 
                 Hs.548513 
                 −1.06 
                 0.67 
               
               
                 129320 
                 FRAS1 
                 1.17 
                 0.67 
                 76182 
                 CCDC3 
                 −1.06 
                 0.67 
               
               
                 43745 
                 SYT6 
                 1.17 
                 0.67 
                 1554367 
                 TXNIP 
                 −1.06 
                 0.67 
               
               
                 204335 
                 CD24 
                 1.16 
                 0.67 
                 454459 
                 FBXL14 
                 −1.04 
                 0.67 
               
               
                 1946026 
                 FLJ10884 
                 1.15 
                 0.67 
                 72003 
                 IL6R 
                 −1.04 
                 0.67 
               
               
                 179534 
                 KCNQ2 
                 1.15 
                 0.67 
                 429093 
                 LOC285458 
                 −1.03 
                 0.67 
               
               
                 898218 
                 IGFBP3 
                 1.14 
                 0.67 
                 810303 
                 Hs.451488 
                 −1.02 
                 0.67 
               
               
                 782476 
                 GULP1 
                 1.13 
                 0.67 
                 120162 
                 Hs.535086 
                 −1.01 
                 0.67 
               
               
                 309929 
                 GPR 
                 1.11 
                 0.67 
                 1324242 
                 TNFSF7 
                 −1.01 
                 0.67 
               
               
                 756372 
                 RARRES2 
                 1.11 
                 0.67 
                 731255 
                 Hs.487536 
                 −1.00 
                 0.67 
               
               
                 1500247 
                 AA886761 
                 1.09 
                 0.67 
                 32576 
                 CCDC3 
                 −0.97 
                 0.67 
               
               
                 281039 
                 FABP5 
                 1.08 
                 0.67 
                 416408 
                 Hs.79856 
                 −0.96 
                 0.67 
               
               
                 79598 
                 CDH1 
                 1.06 
                 0.67 
                 2009000 
                 GNB3 
                 −0.95 
                 0.67 
               
               
                 810728 
                 ZD52F10 
                 1.04 
                 0.67 
                 379768 
                 CRLF1 
                 −0.95 
                 0.67 
               
               
                 1883559 
                 FST 
                 1.04 
                 0.67 
                 1473171 
                 TXNIP 
                 −0.95 
                 0.67 
               
               
                 51807 
                 FHOD3 
                 1.03 
                 0.67 
                 502656 
                 IMPA3 
                 −0.95 
                 0.67 
               
               
                 1607473 
                 Hs.157101 
                 1.01 
                 0.67 
                 594758 
                 Hs.529095 
                 −0.95 
                 0.67 
               
               
                 66977 
                 AIG1 
                 1.01 
                 0.67 
                 260170 
                 N32072 
                 −0.95 
                 0.67 
               
               
                 927112 
                 KIAA0773 
                 1.00 
                 0.67 
                 2028002 
                 ABCD1 
                 −0.94 
                 0.67 
               
               
                 361974 
                 PTN 
                 1.00 
                 0.67 
                 32110 
                 ABCG2 
                 −0.93 
                 0.81 
               
               
                 880630 
                 MGC3036 
                 0.99 
                 0.67 
                 781738 
                 GATA4 
                 −0.93 
                 0.81 
               
               
                 786609 
                 COL12A1 
                 0.99 
                 0.67 
                 296140 
                 MGC15887 
                 −0.93 
                 0.81 
               
               
                 1607129 
                 POU5F1 
                 0.99 
                 0.67 
                 1928791 
                 F3 
                 −0.93 
                 0.81 
               
               
                 210921 
                 NFKBIZ 
                 0.98 
                 0.67 
                 489594 
                 ZCWCC2 
                 −0.92 
                 0.81 
               
               
                 878850 
                 GCAT 
                 0.98 
                 0.67 
                 1257131 
                 Hs.552645 
                 −0.92 
                 0.81 
               
               
                 281100 
                 SYT6 
                 0.98 
                 0.67 
                 243410 
                 GATA4 
                 −0.91 
                 0.81 
               
               
                 788234 
                 ID4 
                 0.96 
                 0.67 
                 685489 
                 Hs.505172 
                 −0.91 
                 0.81 
               
               
                 774446 
                 ADM 
                 0.96 
                 0.67 
                 178825 
                 NRGN 
                 −0.91 
                 0.81 
               
               
                 34140 
                 GCA 
                 0.96 
                 0.67 
                 646057 
                 SPRED2 
                 −0.90 
                 0.81 
               
               
                 743426 
                 KIAA1576 
                 0.96 
                 0.67 
                 431301 
                 CHST2 
                 −0.90 
                 0.81 
               
               
                 307094 
                 GCAT 
                 0.96 
                 0.67 
                 1927991 
                 ENPP2 
                 −0.90 
                 0.81 
               
               
                 666371 
                 THBS1 
                 0.95 
                 0.67 
                 1895676 
                 BARX1 
                 −0.90 
                 0.81 
               
               
                 81331 
                 FABP5 
                 0.94 
                 0.67 
                 951303 
                 AA620527 
                 −0.90 
                 0.81 
               
               
                 282587 
                 CA11 
                 0.94 
                 0.67 
                 1460653 
                 SEPT6 
                 −0.89 
                 0.81 
               
               
                 283995 
                 PAR1 
                 0.94 
                 0.67 
                 810612 
                 S100A11 
                 −0.89 
                 0.81 
               
               
                 251019 
                 CDH1 
                 0.94 
                 0.67 
                 60249 
                 SFTPC 
                 −0.89 
                 0.81 
               
               
                 359684 
                 ZDHHC22 
                 0.94 
                 0.67 
                 294537 
                 RAB17 
                 −0.89 
                 0.81 
               
               
                 502664 
                 RIS1 
                 0.94 
                 0.67 
                 1324885 
                 LOC284542 
                 −0.89 
                 0.81 
               
               
                 681865 
                 C13orf25 
                 0.93 
                 0.67 
                 756931 
                 S100A1 
                 −0.89 
                 0.81 
               
               
                 230882 
                 PAX6 
                 0.93 
                 0.67 
                 1585518 
                 KIAA1442 
                 −0.88 
                 0.81 
               
               
                 768448 
                 JPH4 
                 0.93 
                 0.67 
                 379598 
                 TRPV4 
                 −0.87 
                 0.81 
               
               
                 502446 
                 DNAPTP6 
                 0.93 
                 0.67 
                 813631 
                 TM7SF3 
                 −0.87 
                 0.81 
               
               
                 1911780 
                 TCF7L2 
                 0.92 
                 0.67 
                 1630411 
                 TDE1 
                 −0.87 
                 0.81 
               
               
                 24271 
                 TOX 
                 0.92 
                 0.67 
                 1456122 
                 THEA 
                 −0.86 
                 0.81 
               
               
                 342640 
                 KIAA0101 
                 0.92 
                 0.67 
                 1925681 
                 SMYD2 
                 −0.86 
                 0.81 
               
               
                 141758 
                 Hs.191591 
                 0.92 
                 0.67 
                 133273 
                 PMP22 
                 −0.86 
                 0.81 
               
               
                 434768 
                 FST 
                 0.91 
                 0.67 
                 81316 
                 ARG99 
                 −0.86 
                 0.81 
               
               
                 782835 
                 FOXO1A 
                 0.91 
                 0.67 
                 81409 
                 GABARAPL1 
                 −0.86 
                 0.81 
               
               
                 147925 
                 Hs.298258 
                 0.90 
                 0.67 
                 359835 
                 SAT 
                 −0.85 
                 0.81 
               
               
                 878627 
                 AA775288 
                 0.89 
                 0.81 
                 2010319 
                 NALP1 
                 −0.85 
                 0.81 
               
               
                 877789 
                 LYPDC1 
                 0.88 
                 0.81 
                 1946438 
                 TM7SF3 
                 −0.85 
                 0.81 
               
               
                 137535 
                 TIF1 
                 0.88 
                 0.81 
                 753467 
                 SLC2A3 
                 −0.85 
                 0.81 
               
               
                 282977 
                 ADCY2 
                 0.88 
                 0.81 
                 435566 
                 NOS3AS 
                 −0.85 
                 0.81 
               
               
                 1551722 
                 AA922660 
                 0.88 
                 0.81 
                 42893 
                 R59724 
                 −0.84 
                 0.81 
               
               
                 743829 
                 RGMA 
                 0.88 
                 0.81 
                 154172 
                 FCGBP 
                 −0.84 
                 0.81 
               
               
                 122982 
                 EGLN3 
                 0.88 
                 0.81 
                 782145 
                 TPTE 
                 −0.84 
                 0.81 
               
               
                 470092 
                 LARGE 
                 0.88 
                 0.81 
                 795841 
                 FLJ14466 
                 −0.84 
                 0.81 
               
               
                 192543 
                 KIAA0773 
                 0.87 
                 0.81 
                 796398 
                 PEG3 
                 −0.84 
                 0.81 
               
               
                 1912578 
                 PTGIS 
                 0.87 
                 0.81 
                 754017 
                 C12orf4 
                 −0.83 
                 0.81 
               
               
                 810041 
                 SS18 
                 0.86 
                 0.81 
                 340745 
                 Hs.371609 
                 −0.83 
                 0.81 
               
               
                 68265 
                 AFP 
                 0.86 
                 0.81 
                 898298 
                 PRKAB2 
                 −0.83 
                 0.81 
               
               
                 789369 
                 ID4 
                 0.86 
                 0.81 
                 1558625 
                 Hs.371609 
                 −0.83 
                 0.81 
               
               
                 1534890 
                 ANKRD12 
                 0.86 
                 0.81 
                 789253 
                 PSEN2 
                 −0.83 
                 0.81 
               
               
                 770462 
                 CPZ 
                 0.86 
                 0.81 
                 357298 
                 Hs.550621 
                 −0.83 
                 1.12 
               
               
                 758298 
                 TOX 
                 0.85 
                 0.81 
                 1554451 
                 GJC1 
                 −0.83 
                 1.12 
               
               
                 417800 
                 Hs.59203 
                 0.85 
                 0.81 
                 795758 
                 DKFZP434B044 
                 −0.82 
                 1.12 
               
               
                 797059 
                 AA463250 
                 0.85 
                 0.81 
                 825343 
                 MGC15887 
                 −0.82 
                 1.12 
               
               
                 341328 
                 TPM1 
                 0.84 
                 0.81 
                 897865 
                 MID1 
                 −0.82 
                 1.12 
               
               
                 34934 
                 R45160 
                 0.84 
                 0.81 
                 683569 
                 AA215397 
                 −0.82 
                 1.12 
               
               
                 812277 
                 PLXDC2 
                 0.84 
                 0.81 
                 252663 
                 CALB1 
                 −0.82 
                 1.12 
               
               
                 281908 
                 COL8A1 
                 0.84 
                 0.81 
                 306933 
                 C9orf25 
                 −0.82 
                 1.12 
               
               
                 504337 
                 HESX1 
                 0.83 
                 0.81 
                 461690 
                 ACTR1B 
                 −0.82 
                 1.12 
               
               
                 796569 
                 C17 
                 0.83 
                 0.81 
                 2009885 
                 BCAT1 
                 −0.81 
                 1.12 
               
               
                 825369 
                 VGLL4 
                 0.83 
                 0.81 
                 486493 
                 GPR124 
                 −0.81 
                 1.12 
               
               
                 809707 
                 JUNB 
                 0.83 
                 0.81 
                 510576 
                 AGR2 
                 −0.81 
                 1.12 
               
               
                 2306765 
                 C18orf43 
                 0.83 
                 0.81 
                 841655 
                 JARID1A 
                 −0.81 
                 1.12 
               
               
                 40963 
                 Hs.171485 
                 0.83 
                 0.81 
                 564803 
                 FOXM1 
                 −0.81 
                 1.12 
               
               
                 151477 
                 FLJ38507 
                 0.82 
                 0.81 
                 324785 
                 P4HA2 
                 −0.81 
                 1.12 
               
               
                 2010012 
                 LRRC17 
                 0.82 
                 0.81 
                 826103 
                 AA521416 
                 −0.81 
                 1.12 
               
               
                 132637 
                 GCA 
                 0.82 
                 0.81 
                 66978 
                 T67547 
                 −0.81 
                 1.12 
               
               
                 309864 
                 JUNB 
                 0.82 
                 0.81 
                 1632011 
                 NPR2 
                 −0.80 
                 1.12 
               
               
                 753162 
                 TBC1D4 
                 0.82 
                 0.81 
                 854189 
                 AA669383 
                 −0.80 
                 1.12 
               
               
                 51255 
                 Hs.126110 
                 0.82 
                 0.81 
                 279496 
                 DND1 
                 −0.80 
                 1.12 
               
               
                 32962 
                 Hs.22545 
                 0.81 
                 0.81 
                 45623 
                 SMYD2 
                 −0.80 
                 1.12 
               
               
                 782688 
                 DNALI1 
                 0.81 
                 0.81 
                 1322814 
                 AA745659 
                 −0.80 
                 1.12 
               
               
                 436070 
                 CA14 
                 0.81 
                 0.81 
                 744001 
                 RBM5 
                 −0.80 
                 1.12 
               
               
                 202535 
                 H19 
                 0.80 
                 1.12 
                 305895 
                 Hs.180171 
                 −0.79 
                 1.12 
               
               
                 811028 
                 VMP1 
                 0.80 
                 1.12 
                 491232 
                 PSEN2 
                 −0.79 
                 1.12 
               
               
                 144834 
                 MAP7 
                 0.80 
                 1.12 
                 1492891 
                 ARF4L 
                 −0.79 
                 1.12 
               
               
                 814769 
                 MLF1IP 
                 0.80 
                 1.12 
                 51548 
                 H20826 
                 −0.79 
                 1.12 
               
               
                 447786 
                 AUTS2 
                 0.80 
                 1.12 
                 1588349 
                 IMPA3 
                 −0.79 
                 1.12 
               
               
                 727268 
                 Hs.545676 
                 0.80 
                 1.12 
                 121981 
                 SLC2A14 
                 −0.79 
                 1.12 
               
               
                 971188 
                 AA774927 
                 0.80 
                 1.12 
                 878572 
                 NET-5 
                 −0.79 
                 1.12 
               
               
                 810218 
                 OCIAD2 
                 0.80 
                 1.12 
                 2018581 
                 IL6ST 
                 −0.79 
                 1.12 
               
               
                 50114 
                 PCDHA6 
                 0.80 
                 1.12 
                 154138 
                 MBTPS2 
                 −0.79 
                 1.34 
               
               
                 878630 
                 NBEA 
                 0.79 
                 1.12 
                 853962 
                 AA644695 
                 −0.79 
                 1.34 
               
               
                 360787 
                 TIF1 
                 0.79 
                 1.12 
                 1916973 
                 NDUFA9 
                 −0.79 
                 1.34 
               
               
                 52430 
                 SALL2 
                 0.79 
                 1.12 
                 49145 
                 Hs.494030 
                 −0.79 
                 1.34 
               
               
                 1696831 
                 AI095794 
                 0.79 
                 1.12 
                 1554439 
                 Hs.550811 
                 −0.79 
                 1.34 
               
               
                 760231 
                 USP9X 
                 0.79 
                 1.12 
                 1475308 
                 Hs.546579 
                 −0.78 
                 1.34 
               
               
                 221295 
                 ID2 
                 0.79 
                 1.12 
                 131979 
                 EPAS1 
                 −0.78 
                 1.34 
               
               
                 345601 
                 D2S448 
                 0.79 
                 1.12 
                 1455745 
                 ZDHHC9 
                 −0.78 
                 1.34 
               
               
                 897656 
                 FARP1 
                 0.79 
                 1.12 
                 768944 
                 PGK1 
                 −0.78 
                 1.34 
               
               
                 813265 
                 NFIB 
                 0.79 
                 1.12 
                 757152 
                 ZNF318 
                 −0.78 
                 1.34 
               
               
                 27069 
                 SCLY 
                 0.78 
                 1.12 
                 162199 
                 PTPRM 
                 −0.78 
                 1.34 
               
               
                 809694 
                 CRABP1 
                 0.78 
                 1.12 
                 855786 
                 WARS 
                 −0.78 
                 1.34 
               
               
                 726779 
                 CNN1 
                 0.78 
                 1.34 
                 502778 
                 LRP6 
                 −0.78 
                 1.34 
               
               
                 279577 
                 Hs.46551 
                 0.77 
                 1.34 
                 1434905 
                 HOXB7 
                 −0.78 
                 1.34 
               
               
                 280758 
                 TMSB4Y 
                 0.77 
                 1.34 
                 489677 
                 UPP1 
                 −0.77 
                 1.34 
               
               
                 35626 
                 SLC38A1 
                 0.77 
                 1.34 
                 124071 
                 ASB9 
                 −0.77 
                 1.34 
               
               
                 252830 
                 H88050 
                 0.77 
                 1.34 
                 296020 
                 Hs.522906 
                 −0.77 
                 1.34 
               
               
                 854879 
                 SPHK2 
                 0.77 
                 1.34 
                 191516 
                 CREBBP 
                 −0.77 
                 1.34 
               
               
                 882402 
                 KIAA0692 
                 0.77 
                 1.34 
                 380620 
                 PSEN2 
                 −0.77 
                 1.34 
               
               
                 486436 
                 UGP2 
                 0.77 
                 1.34 
                 1732666 
                 AI191823 
                 −0.77 
                 1.34 
               
               
                 31475 
                 SALL3 
                 0.77 
                 1.34 
                 825270 
                 PREX1 
                 −0.77 
                 1.34 
               
               
                 666451 
                 PSD3 
                 0.77 
                 1.34 
                 247546 
                 VTN 
                 −0.77 
                 1.34 
               
               
                 379709 
                 LRRN1 
                 0.76 
                 1.34 
                 77651 
                 HDAC6 
                 −0.77 
                 1.34 
               
               
                 628357 
                 ACTN3 
                 0.76 
                 1.34 
                 1637233 
                 TFCP2L1 
                 −0.77 
                 1.34 
               
               
                 2314305 
                 CDKN1C 
                 0.76 
                 1.34 
                 1323328 
                 PTHR1 
                 −0.77 
                 1.34 
               
               
                 1567985 
                 AA975922 
                 0.76 
                 1.34 
                 586803 
                 PGF 
                 −0.76 
                 1.34 
               
               
                 344036 
                 BNC2 
                 0.76 
                 1.34 
                 377560 
                 CD3D 
                 −0.76 
                 1.34 
               
               
                 843036 
                 MAP7 
                 0.76 
                 1.34 
                 1470131 
                 TFCP2L1 
                 −0.76 
                 1.34 
               
               
                 782737 
                 USP44 
                 0.76 
                 1.34 
                 83444 
                 SLC10A1 
                 −0.76 
                 1.34 
               
               
                 341310 
                 FRZB 
                 0.76 
                 2.27 
                 154600 
                 PLCD1 
                 −0.76 
                 1.34 
               
               
                 731025 
                 PPM1E 
                 0.75 
                 2.27 
                 1472405 
                 S100A10 
                 −0.76 
                 1.34 
               
               
                 282717 
                 BCL2 
                 0.75 
                 2.27 
                 1456120 
                 GRK5 
                 −0.76 
                 1.34 
               
               
                 50354 
                 OTX2 
                 0.74 
                 2.27 
                 214996 
                 FRS2 
                 −0.76 
                 2.27 
               
               
                 755444 
                 TMSB4X 
                 0.74 
                 2.27 
                 85313 
                 CCPG1 
                 −0.75 
                 2.27 
               
               
                 289936 
                 Hs.390594 
                 0.74 
                 2.27 
                 295831 
                 DERA 
                 −0.75 
                 2.27 
               
               
                 27396 
                 GAL3ST3 
                 0.74 
                 2.27 
                 296623 
                 Hs.431518 
                 −0.75 
                 2.27 
               
               
                 788667 
                 PLEKHA9 
                 0.74 
                 2.27 
                 711918 
                 QPCT 
                 −0.75 
                 2.27 
               
               
                 1049291 
                 OR7E47P 
                 0.74 
                 2.27 
                 1732811 
                 TULP3 
                 −0.75 
                 2.27 
               
               
                 328542 
                 GALNT3 
                 0.74 
                 2.27 
                 784296 
                 NR3C2 
                 −0.75 
                 2.27 
               
               
                 725395 
                 UBE2L6 
                 0.73 
                 2.27 
                 809719 
                 URB 
                 −0.75 
                 2.27 
               
               
                 1895357 
                 AI299356 
                 0.73 
                 2.27 
                 284076 
                 CREBL2 
                 −0.75 
                 2.27 
               
               
                 1456776 
                 CLDN4 
                 0.73 
                 2.27 
                 1552602 
                 PHKA1 
                 −0.74 
                 2.27 
               
               
                 758088 
                 CALD1 
                 0.73 
                 2.27 
                 756595 
                 S100A10 
                 −0.74 
                 2.27 
               
               
                 340657 
                 LEFTY2 
                 0.73 
                 2.27 
                 682418 
                 ELF4 
                 −0.74 
                 2.27 
               
               
                 365147 
                 ERBB2 
                 0.73 
                 2.27 
                 811072 
                 Hs.217583 
                 −0.74 
                 2.27 
               
               
                 1855229 
                 Hs.149796 
                 0.73 
                 2.27 
                 488301 
                 LOC149603 
                 −0.74 
                 2.27 
               
               
                 753291 
                 C1orf21 
                 0.73 
                 2.27 
                 752557 
                 GPSM3 
                 −0.74 
                 2.27 
               
               
                 50499 
                 MGC72075 
                 0.73 
                 2.27 
                 567127 
                 FLJ20716 
                 −0.74 
                 2.27 
               
               
                 126458 
                 MT1K 
                 0.72 
                 2.27 
                 1555659 
                 AI147534 
                 −0.74 
                 2.27 
               
               
                 740851 
                 Hs.479288 
                 0.72 
                 2.27 
                 897301 
                 CMAS 
                 −0.74 
                 2.27 
               
               
                 609155 
                 LRRN1 
                 0.72 
                 2.27 
                 754559 
                 C2orf27 
                 −0.73 
                 2.27 
               
               
                 324437 
                 CXCL1 
                 0.72 
                 2.70 
                 23819 
                 ABCG1 
                 −0.73 
                 2.27 
               
               
                 203003 
                 NME4 
                 0.72 
                 2.70 
                 1917493 
                 SCAND2 
                 −0.73 
                 2.27 
               
               
                 566597 
                 PRSS16 
                 0.72 
                 2.70 
                 753775 
                 GMPR 
                 −0.73 
                 2.27 
               
               
                 194706 
                 USP9X 
                 0.72 
                 2.70 
                 1558655 
                 ASRGL1 
                 −0.73 
                 2.27 
               
               
                 783729 
                 ERBB2 
                 0.72 
                 2.70 
                 1858444 
                 MDM4 
                 −0.73 
                 2.27 
               
               
                 755689 
                 RARG 
                 0.72 
                 2.70 
                 454341 
                 MYL4 
                 −0.73 
                 2.27 
               
               
                 214858 
                 LDB2 
                 0.72 
                 2.70 
                 813520 
                 BPHB3 
                 −0.73 
                 2.27 
               
               
                 149743 
                 C15orf29 
                 0.72 
                 2.70 
                 293336 
                 N64734 
                 −0.73 
                 2.27 
               
               
                 137387 
                 TFAP2A 
                 0.71 
                 2.70 
                 289794 
                 C12orf2 
                 −0.73 
                 2.27 
               
               
                 626793 
                 NIPA2 
                 0.71 
                 2.70 
                 1526826 
                 HOXB2 
                 −0.73 
                 2.27 
               
               
                 858401 
                 SCG3 
                 0.71 
                 2.70 
                 1126568 
                 Hs.116314 
                 −0.73 
                 2.27 
               
               
                 80643 
                 EDIL3 
                 0.71 
                 2.70 
                 397488 
                 TBX3 
                 −0.73 
                 2.27 
               
               
                 1551239 
                 FLJ10884 
                 0.71 
                 2.70 
                 713566 
                 MSP 
                 −0.72 
                 2.27 
               
               
                 39824 
                 UNC13A 
                 0.71 
                 2.70 
                 267460 
                 CGI-141 
                 −0.72 
                 2.27 
               
               
                 301878 
                 SCGB3A2 
                 0.71 
                 2.70 
                 1570663 
                 FKBP4 
                 −0.72 
                 2.70 
               
               
                 1605321 
                 C20orf24 
                 0.71 
                 2.70 
                 1585211 
                 Hs.194678 
                 −0.72 
                 2.70 
               
               
                 277165 
                 TMEFF1 
                 0.71 
                 2.70 
                 259884 
                 GPR126 
                 −0.71 
                 2.70 
               
               
                 347520 
                 BOC 
                 0.71 
                 2.70 
                 148469 
                 TYROBP 
                 −0.71 
                 2.70 
               
               
                 812088 
                 NLN 
                 0.71 
                 2.70 
                 1855351 
                 EPSTI1 
                 −0.71 
                 2.70 
               
               
                 1607198 
                 FSIP1 
                 0.71 
                 2.70 
                 1476466 
                 KBTBD9 
                 −0.71 
                 2.70 
               
               
                 1500643 
                 SLC13A1 
                 0.71 
                 2.70 
                 298189 
                 Hs.171806 
                 −0.71 
                 2.70 
               
               
                 298702 
                 APOM 
                 0.70 
                 2.70 
                 940994 
                 Hs.105316 
                 −0.71 
                 2.70 
               
               
                 347035 
                 KIAA0476 
                 0.70 
                 2.70 
                 1588935 
                 PHLDA3 
                 −0.71 
                 2.70 
               
               
                 293569 
                 C1orf21 
                 0.70 
                 2.70 
                 346696 
                 TEAD4 
                 −0.70 
                 2.70 
               
               
                 309447 
                 TM4SF10 
                 0.70 
                 2.70 
                 304975 
                 KIAA0318 
                 −0.70 
                 2.70 
               
               
                 22778 
                 R38615 
                 0.70 
                 2.70 
                 45464 
                 AK2 
                 −0.70 
                 2.70 
               
               
                 324690 
                 GREM1 
                 0.70 
                 2.70 
                 143997 
                 PSMD10 
                 −0.70 
                 2.70 
               
               
                 134712 
                 SLC7A1 
                 0.70 
                 2.70 
                 789147 
                 ENO2 
                 −0.70 
                 2.70 
               
               
                 785941 
                 ZNF278 
                 0.70 
                 2.70 
                 949939 
                 PGK1 
                 −0.70 
                 2.70 
               
               
                 34901 
                 DOK5 
                 0.70 
                 2.70 
                 210789 
                 AGT 
                 −0.70 
                 2.70 
               
               
                 491311 
                 EGLN3 
                 0.70 
                 2.70 
                 1865128 
                 PEX5 
                 −0.70 
                 2.70 
               
               
                 41103 
                 TTYH1 
                 0.70 
                 2.70 
                 730150 
                 LOC144363 
                 −0.70 
                 2.70 
               
               
                 813608 
                 Hs.346566 
                 0.70 
                 2.70 
                 727251 
                 CD9 
                 −0.70 
                 2.70 
               
               
                 257109 
                 USP9X 
                 0.69 
                 2.70 
                 281053 
                 C2orf18 
                 −0.70 
                 2.70 
               
               
                 488207 
                 T1A-2 
                 0.69 
                 2.70 
                 743810 
                 CDCA3 
                 −0.70 
                 2.70 
               
               
                 782826 
                 BACH 
                 0.69 
                 2.70 
                 280970 
                 NOL1 
                 −0.69 
                 2.99 
               
               
                 417226 
                 MYC 
                 0.69 
                 2.70 
                 361456 
                 DDIT3 
                 −0.69 
                 2.99 
               
               
                 323238 
                 CXCL1 
                 0.69 
                 2.70 
                 271219 
                 Hs.487393 
                 −0.69 
                 2.99 
               
               
                 37980 
                 ZIC2 
                 0.69 
                 2.70 
                 1682167 
                 MGC5370 
                 −0.69 
                 2.99 
               
               
                 628955 
                 FOXO1A 
                 0.69 
                 2.70 
                 283089 
                 LOC340542 
                 −0.69 
                 2.99 
               
               
                 1472735 
                 MT1E 
                 0.69 
                 2.70 
                 1635359 
                 RASD1 
                 −0.68 
                 2.99 
               
               
                 813628 
                 SCN2B 
                 0.69 
                 2.70 
                 309776 
                 CFLAR 
                 −0.68 
                 2.99 
               
               
                 45542 
                 IGFBP5 
                 0.69 
                 2.70 
                 206795 
                 ASGR2 
                 −0.68 
                 2.99 
               
               
                 141768 
                 ERBB2 
                 0.69 
                 2.99 
                 40871 
                 C3F 
                 −0.68 
                 2.99 
               
               
                 701115 
                 C6orf115 
                 0.69 
                 2.99 
                 742642 
                 MIG-6 
                 −0.68 
                 2.99 
               
               
                 1635970 
                 MFHAS1 
                 0.69 
                 2.99 
                 202498 
                 IL10RB 
                 −0.68 
                 2.99 
               
               
                 377461 
                 CAV1 
                 0.69 
                 2.99 
                 855523 
                 GPX3 
                 −0.68 
                 2.99 
               
               
                 173228 
                 GMFB 
                 0.68 
                 2.99 
                 1587065 
                 RPESP 
                 −0.68 
                 2.99 
               
               
                 739193 
                 CRABP1 
                 0.68 
                 2.99 
                 767041 
                 FLJ41841 
                 −0.68 
                 2.99 
               
               
                 29828 
                 TGFB1I4 
                 0.68 
                 2.99 
                 359982 
                 AA035669 
                 −0.68 
                 2.99 
               
               
                 842918 
                 FARP1 
                 0.68 
                 2.99 
                 1692195 
                 KIFAP3 
                 −0.68 
                 2.99 
               
               
                 127486 
                 LDHD 
                 0.68 
                 2.99 
                 505243 
                 ITPR2 
                 −0.68 
                 2.99 
               
               
                 51920 
                 OSBPL1A 
                 0.68 
                 2.99 
                 949938 
                 CST3 
                 −0.68 
                 2.99 
               
               
                 51378 
                 Hs.31924 
                 0.68 
                 2.99 
                 2010188 
                 CCL26 
                 −0.68 
                 2.99 
               
               
                 506060 
                 Hs.506182 
                 0.67 
                 2.99 
                 1734754 
                 LEPREL2 
                 −0.68 
                 2.99 
               
               
                 1865374 
                 EFCBP2 
                 0.67 
                 2.99 
                 142326 
                 FLJ90036 
                 −0.67 
                 2.99 
               
               
                 2052032 
                 MYO10 
                 0.67 
                 2.99 
                 256947 
                 NRK 
                 −0.67 
                 2.99 
               
               
                 752652 
                 TCF7L2 
                 0.67 
                 2.99 
                 1562645 
                 NFKB2 
                 −0.67 
                 2.99 
               
               
                 1457205 
                 LOC152195 
                 0.67 
                 2.99 
                 1168484 
                 KITLG 
                 −0.67 
                 2.99 
               
               
                 50562 
                 C8orf4 
                 0.67 
                 2.99 
                 1641822 
                 WBP11 
                 −0.67 
                 2.99 
               
               
                 133136 
                 DEK 
                 0.67 
                 2.99 
                 609929 
                 DDX47 
                 −0.67 
                 2.99 
               
               
                 844680 
                 TRD@ 
                 0.67 
                 2.99 
                 1476157 
                 PEX5 
                 −0.67 
                 2.99 
               
               
                 825382 
                 DCP2 
                 0.67 
                 2.99 
                 433253 
                 FBP1 
                 −0.67 
                 2.99 
               
               
                 80823 
                 RPL10A 
                 0.67 
                 2.99 
                 1943018 
                 IRAK1 
                 −0.67 
                 2.99 
               
               
                 502287 
                 EMB 
                 0.67 
                 2.99 
                 134430 
                 C9orf13 
                 −0.67 
                 2.99 
               
               
                 809603 
                 PTMA 
                 0.67 
                 2.99 
                 143661 
                 NTN4 
                 −0.67 
                 3.00 
               
               
                 504461 
                 KMO 
                 0.67 
                 2.99 
                 853066 
                 AA668256 
                 −0.67 
                 3.00 
               
               
                 366848 
                 TCF7L2 
                 0.67 
                 2.99 
                 753914 
                 ITPR2 
                 −0.66 
                 3.00 
               
               
                 207107 
                 CALD1 
                 0.66 
                 2.99 
                 752808 
                 TMED4 
                 −0.66 
                 3.00 
               
               
                 74537 
                 AFP 
                 0.66 
                 2.99 
                 1586703 
                 GPR3 
                 −0.66 
                 3.00 
               
               
                 2020772 
                 TM7SF2 
                 0.66 
                 2.99 
                 897987 
                 NDUFA9 
                 −0.66 
                 3.00 
               
               
                 970591 
                 HMGB1 
                 0.66 
                 2.99 
                 429349 
                 RGS4 
                 −0.66 
                 3.00 
               
               
                 1475968 
                 TEAD2 
                 0.66 
                 2.99 
                 813189 
                 TDE1 
                 −0.66 
                 3.00 
               
               
                 81408 
                 C13orf7 
                 0.66 
                 2.99 
                 51373 
                 OMG 
                 −0.66 
                 3.00 
               
               
                 244652 
                 SET 
                 0.66 
                 2.99 
                 194136 
                 H50971 
                 −0.66 
                 3.00 
               
               
                 1586535 
                 Hs.120204 
                 0.66 
                 2.99 
                 429368 
                 TLX1 
                 −0.66 
                 3.00 
               
               
                 230100 
                 Hs.546672 
                 0.66 
                 2.99 
                 859912 
                 TDE1 
                 −0.66 
                 3.00 
               
               
                 502155 
                 PTGIS 
                 0.66 
                 2.99 
                 1627688 
                 LMO6 
                 −0.66 
                 3.00 
               
               
                 293032 
                 TFAP2A 
                 0.66 
                 2.99 
                 80162 
                 RAD51C 
                 −0.66 
                 3.00 
               
               
                 283398 
                 TM4SF10 
                 0.66 
                 2.99 
                 877832 
                 AA625628 
                 −0.66 
                 3.00 
               
               
                 327593 
                 Hs.547695 
                 0.66 
                 2.99 
                 1896981 
                 XCL1 
                 −0.66 
                 3.00 
               
               
                 208718 
                 ANXA1 
                 0.66 
                 3.00 
                 1670954 
                 KIAA1363 
                 −0.65 
                 3.00 
               
               
                 265694 
                 OLFML2B 
                 0.66 
                 3.00 
                 1635221 
                 ETNK1 
                 −0.65 
                 3.00 
               
               
                 291448 
                 SILV 
                 0.65 
                 3.00 
                 1501914 
                 P4HB 
                 −0.65 
                 3.00 
               
               
                 592594 
                 LRIG1 
                 0.65 
                 3.00 
                 1879169 
                 RAB21 
                 −0.65 
                 3.00 
               
               
                 137984 
                 FLJ38507 
                 0.65 
                 3.00 
                 813426 
                 TRIB2 
                 −0.65 
                 3.00 
               
               
                 1761751 
                 MAPK8IP1 
                 0.65 
                 3.00 
                 727988 
                 CDW52 
                 −0.65 
                 3.00 
               
               
                 1881469 
                 Hs.547698 
                 0.65 
                 3.00 
                 302632 
                 B7 
                 −0.65 
                 3.00 
               
               
                 134783 
                 COL11A1 
                 0.65 
                 3.00 
                 869187 
                 EPAS1 
                 −0.65 
                 3.00 
               
               
                 726658 
                 NME3 
                 0.65 
                 3.00 
                 52031 
                 LOC126731 
                 −0.65 
                 3.00 
               
               
                 239256 
                 FZD7 
                 0.65 
                 3.00 
                 43865 
                 DNCI1 
                 −0.65 
                 3.00 
               
               
                 284007 
                 LOC152485 
                 0.65 
                 3.00 
                 1724716 
                 TTLL3 
                 −0.65 
                 3.00 
               
               
                 788641 
                 AP1S2 
                 0.64 
                 3.00 
                 124737 
                 CHST12 
                 −0.65 
                 3.00 
               
               
                 878583 
                 CABP1 
                 0.64 
                 3.00 
                 234348 
                 MXD3 
                 −0.64 
                 3.00 
               
               
                 854570 
                 TEAD2 
                 0.64 
                 3.00 
                 1500631 
                 DDIT3 
                 −0.64 
                 3.00 
               
               
                 714106 
                 PLAU 
                 0.64 
                 3.00 
                 1609537 
                 WNK1 
                 −0.64 
                 3.00 
               
               
                 880747 
                 MGC3036 
                 0.64 
                 3.00 
                 328821 
                 CFC1 
                 −0.64 
                 3.00 
               
               
                 782576 
                 Hs.459026 
                 0.64 
                 3.00 
                 842826 
                 RBBP4 
                 −0.64 
                 3.00 
               
               
                 47359 
                 EDN1 
                 0.64 
                 3.00 
                 2308429 
                 PPFIA4 
                 −0.64 
                 3.00 
               
               
                 1475734 
                 TOX 
                 0.64 
                 3.00 
                 1566554 
                 PRKAB2 
                 −0.64 
                 3.00 
               
               
                 1857589 
                 AI269390 
                 0.64 
                 3.00 
                 810552 
                 REA 
                 −0.64 
                 3.00 
               
               
                 1604674 
                 ZIC2 
                 0.64 
                 3.00 
                 253733 
                 FOXC1 
                 −0.64 
                 3.00 
               
               
                 1574074 
                 KIAA1586 
                 0.64 
                 3.00 
                 357190 
                 MGC8902 
                 −0.64 
                 3.00 
               
               
                 453602 
                 CALD1 
                 0.64 
                 3.00 
                 162310 
                 PMP22 
                 −0.64 
                 3.00 
               
               
                 814353 
                 AA458838 
                 0.64 
                 3.00 
                 1695674 
                 HSPB6 
                 −0.64 
                 3.00 
               
               
                 1700916 
                 C9orf39 
                 0.64 
                 3.00 
                 289570 
                 NSMAF 
                 −0.64 
                 3.00 
               
               
                 1948377 
                 OPRS1 
                 0.64 
                 3.00 
                 66327 
                 CR1L 
                 −0.64 
                 3.00 
               
               
                 740925 
                 INDO 
                 0.64 
                 3.00 
                 345103 
                 EPHB2 
                 −0.64 
                 3.00 
               
               
                 179266 
                 CTXN1 
                 0.64 
                 3.00 
                 687667 
                 Hs.537002 
                 −0.64 
                 3.66 
               
               
                 79935 
                 T61475 
                 0.64 
                 3.00 
                 856447 
                 IFI30 
                 −0.64 
                 3.66 
               
               
                 24415 
                 TP53 
                 0.64 
                 3.00 
                 297212 
                 ITLN1 
                 −0.64 
                 3.66 
               
               
                 1897950 
                 C15orf29 
                 0.64 
                 3.00 
                 1558505 
                 LEPRE1 
                 −0.64 
                 3.66 
               
               
                 627226 
                 SLC30A1 
                 0.63 
                 3.00 
                 1473168 
                 ZC3HDC6 
                 −0.64 
                 3.66 
               
               
                 1492411 
                 EIF5A 
                 0.63 
                 3.00 
                 1661677 
                 RIF1 
                 −0.63 
                 3.66 
               
               
                 854581 
                 TCF4 
                 0.63 
                 3.00 
                 1636900 
                 AI000268 
                 −0.63 
                 3.66 
               
               
                 241985 
                 PAR1 
                 0.63 
                 3.00 
                 345916 
                 SPTBN1 
                 −0.63 
                 3.66 
               
               
                 1606557 
                 FHL2 
                 0.63 
                 3.00 
                 395400 
                 MBD6 
                 −0.63 
                 3.66 
               
               
                 276574 
                 FLJ36754 
                 0.63 
                 3.66 
                 279970 
                 ADORA2A 
                 −0.63 
                 3.66 
               
               
                 366093 
                 ZNF397 
                 0.63 
                 3.66 
                 1671108 
                 AI075256 
                 −0.63 
                 3.66 
               
               
                 1605008 
                 IGSF4C 
                 0.63 
                 3.66 
                 133988 
                 ACSL4 
                 −0.63 
                 3.66 
               
               
                 1160531 
                 ERBB3 
                 0.63 
                 3.66 
                 377987 
                 ADAMTS15 
                 −0.63 
                 3.66 
               
               
                 565075 
                 STC1 
                 0.63 
                 3.66 
                 729964 
                 SMPD1 
                 −0.63 
                 3.66 
               
               
                 1570558 
                 AA932334 
                 0.63 
                 3.66 
                 2009974 
                 ACHE 
                 −0.63 
                 3.66 
               
               
                 739155 
                 CDH6 
                 0.63 
                 3.66 
                 812961 
                 SIPA1L2 
                 −0.63 
                 3.66 
               
               
                 739159 
                 BPHL 
                 0.63 
                 3.66 
                 810743 
                 MLF2 
                 −0.63 
                 3.66 
               
               
                 488246 
                 KIAA1913 
                 0.63 
                 3.66 
                 1554420 
                 TCEA2 
                 −0.63 
                 3.66 
               
               
                 137297 
                 PGAP1 
                 0.63 
                 3.66 
                 132702 
                 P4HB 
                 −0.63 
                 3.66 
               
               
                 271670 
                 TNFSF13 
                 0.63 
                 3.66 
                 1589083 
                 DEFB1 
                 −0.62 
                 3.66 
               
               
                 324307 
                 TM4SF10 
                 0.63 
                 3.66 
                 1644045 
                 TULP3 
                 −0.62 
                 3.66 
               
               
                 347331 
                 SNTB1 
                 0.63 
                 3.66 
                 770785 
                 MAN1C1 
                 −0.62 
                 3.66 
               
               
                 282895 
                 LRRC16 
                 0.62 
                 3.66 
                 1475648 
                 TTN 
                 −0.62 
                 3.66 
               
               
                 250678 
                 FLJ20171 
                 0.62 
                 3.66 
                 299603 
                 AI822111 
                 −0.62 
                 3.66 
               
               
                 1371759 
                 CUGBP2 
                 0.62 
                 3.66 
                 1917063 
                 SDSL 
                 −0.62 
                 3.66 
               
               
                 725365 
                 GAS1 
                 0.62 
                 3.66 
                 1759254 
                 STS-1 
                 −0.62 
                 3.66 
               
               
                 2005924 
                 MATK 
                 0.62 
                 3.66 
                 127370 
                 R08549 
                 −0.62 
                 3.66 
               
               
                 795746 
                 MLF1IP 
                 0.62 
                 3.66 
                 26482 
                 ZNF335 
                 −0.62 
                 3.66 
               
               
                 1895737 
                 Hs.445295 
                 0.62 
                 3.66 
                 811162 
                 FMOD 
                 −0.62 
                 3.66 
               
               
                 742776 
                 YPEL1 
                 0.62 
                 3.66 
                 79562 
                 MOSPD1 
                 −0.62 
                 3.66 
               
               
                 236338 
                 TP53 
                 0.62 
                 3.66 
                 50166 
                 OATL1 
                 −0.62 
                 3.66 
               
               
                 686667 
                 GCDH 
                 0.62 
                 3.66 
                 1160995 
                 ERF 
                 −0.62 
                 3.66 
               
               
                 180520 
                 UBE3A 
                 0.62 
                 3.66 
                 40040 
                 KIAA1126 
                 −0.61 
                 3.66 
               
               
                 447509 
                 HLA-DOA 
                 0.62 
                 3.66 
                 2296063 
                 KIAA0528 
                 −0.61 
                 3.66 
               
               
                 1862529 
                 Hs.433460 
                 0.62 
                 3.66 
               
               
                 47460 
                 B3GAT1 
                 0.62 
                 3.66 
               
               
                 345645 
                 PDGFB 
                 0.62 
                 3.66 
               
               
                 489169 
                 C10orf83 
                 0.62 
                 3.66 
               
               
                 755299 
                 IER2 
                 0.61 
                 3.66 
               
               
                 504774 
                 GGTLA1 
                 0.61 
                 3.66 
               
               
                 1602927 
                 MGC35048 
                 0.61 
                 3.66 
               
               
                 213850 
                 FJX1 
                 0.61 
                 3.66 
               
               
                 38618 
                 Hs.530150 
                 0.61 
                 3.66 
               
               
                 125187 
                 ERCC2 
                 0.61 
                 3.66 
               
               
                 300099 
                 TM4SF9 
                 0.61 
                 3.66 
               
               
                 153646 
                 R48843 
                 0.61 
                 3.66 
               
               
                 768417 
                 EPB41L3 
                 0.61 
                 3.66 
               
               
                 133518 
                 MAPRE2 
                 0.61 
                 3.66 
               
               
                 1556401 
                 AA936454 
                 0.61 
                 3.66 
               
               
                   
               
               
                 By a simple ranking test (one-class significant analysis of microarrays), 328 genes were identified with highest level and 313 genes with lowest level expression in the ES cells. 
               
               
                 Genes were selected according to the cut-off q value ≦0.05. 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Prostate cancer clinical data and ES type 
               
             
          
           
               
                 Clinical data, Lapointe et al., 2004 (Ref. # 62) 
                   
               
             
          
           
               
                   
                   
                   
                   
                   
                   
                 Recurrence- 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                 free; 
                   
                 This invention 
               
               
                 Patient 
                   
                 Gleason 
                   
                   
                   
                 survival 
                   
                 ES type (b) 
               
             
          
           
               
                 ID (a) 
                 Age 
                 grade 
                 Stage T 
                 Node N 
                 Metastasis M 
                 (months) 
                 Recurrence* 
                 q ≦ 0.01 
                 q ≦ 0.05 
                 q ≦ 0.1 
               
               
                   
               
             
          
           
               
                 PC229 
                 47 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 0.03 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC112 
                 57 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 12.06 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC083 
                 63 
                 4 + 4 
                 T3a 
                 N0 
                 M0 
                 13.6 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC041 
                 54 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 14.2 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC191 
                 59 
                 3 + 3 
                 T3a 
                 N0 
                 M0 
                 15.5 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC111 
                 56 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 17.4 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC187 
                 58 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 2.5 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC028 
                 62 
                 3 + 4 
                 T2b 
                 N0 
                 M0 
                 22.9 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC335 
                 58 
                 3 + 4 
                 T3a 
                 N0 
                 M0 
                 5.6 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC224 
                 64 
                 4 + 3 
                 T3a 
                 N0 
                 M0 
                 5.6 
                 0 
                 1 
                 1 
                 1 
               
               
                 PC100 
                 67 
                 4 + 4 
                 T2b 
                 N0 
                 M0 
                 9 
                 0 
                 0 
                 1 
                 1 
               
               
                 PC087 
                 68 
                 4 + 5 
                 T3a 
                 N0 
                 M0 
                 9.4 
                 0 
                 0 
                 1 
                 1 
               
               
                 PC087 
                 60 
                 4 + 4 
                 T3b 
                 N0 
                 M0 
                 16.2 
                 1 
                 1 
                 1 
                 1 
               
               
                 PC168 
                 50 
                 4 + 5 
                 T2b 
                 N0 
                 M0 
                 17.1 
                 1 
                 1 
                 1 
                 1 
               
               
                 PC019 
                 57 
                 4 + 5 
                 T3a 
                 N1 
                 M0 
                 19.1 
                 1 
                 1 
                 1 
                 1 
               
               
                 PC265 
                 59 
                 4 + 4 
                 T2b 
                 N0 
                 M0 
                 2.76 
                 1 
                 0 
                 1 
                 1 
               
               
                 PC007 
                 56 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 27.7 
                 1 
                 1 
                 1 
                 1 
               
               
                 PC250 
                 55 
                 3 + 3 
                 T3b 
                 N1 
                 M0 
                 3.1 
                 1 
                 1 
                 1 
                 1 
               
               
                 PC103 
                 61 
                 4 + 3 
                 T3a 
                 N0 
                 M0 
                 5.9 
                 1 
                 1 
                 1 
                 1 
               
               
                 PC055 
                 64 
                 4 + 3 
                 T3b 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC130 
                 58 
                 3 + 4 
                 T3a 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC176 
                 67 
                 4 + 4 
                 T3b 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC235 
                 N/A 
                 3 + 3 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC317 
                 58 
                 3 + 3 
                 T2 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC014 
                 N/A 
                 3 + 3 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC027 
                 60 
                 LN meta 
                 T3a 
                 N1 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC054 
                 62 
                 4 + 5 
                 T3b 
                 N1 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC057 
                 61 
                 3 + 4 
                 T2b 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC058 
                 66 
                 3 + 4 
                 T3b 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC114 
                 62 
                 LN meta 
                 T4 
                 Nx 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC115 
                 N/A 
                 LN meta 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC116 
                 58 
                 LN meta 
                 T3 
                 N1 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC118 
                 N/A 
                 LN meta 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC122 
                 66 
                 LN meta 
                 T3 
                 N1 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC129 
                 63 
                 LN meta 
                 T3 
                 N1 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC133 
                 55 
                 LN meta 
                 T3 
                 N1 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC171 
                 50 
                 3 + 3 
                 T3a 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC174 
                 62 
                 3 + 4 
                 T3b 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC180 
                 N/A 
                 3 + 4 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC181 
                 56 
                 4 + 3 
                 T3a 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC194 
                 N/A 
                 LN meta 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC308 
                 59 
                 4 + 5 
                 T3a 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC309 
                 62 
                 4 + 4 
                 T3a 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC310 
                 72 
                 4 + 3 
                 T3a 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC311 
                 48 
                 3 + 3 
                 T3a 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC312 
                 59 
                 3 + 3 
                 T2 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC314 
                 45 
                 3 + 3 
                 T2 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC315 
                 65 
                 4 + 4 
                 T3a 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC316 
                 52 
                 3 + 4 
                 T3a 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC319 
                 58 
                 4 + 4 
                 T3a 
                 N1 
                 Mx 
                 N/A 
                 N/A 
                 1 
                 1 
                 1 
               
               
                 PC126 
                 63 
                 3 + 4 
                 T2a 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 0 
                 1 
                 1 
               
               
                 PC138 
                 60 
                 4 + 4 
                 T3a 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 0 
                 1 
                 1 
               
               
                 PC148 
                 58 
                 3 + 4 
                 T2b 
                 N0 
                 M0 
                 0.03 
                 0 
                 1 
                 0 
                 1 
               
               
                 PC205 
                 66 
                 3 + 4 
                 T2b 
                 N0 
                 M0 
                 0.03 
                 0 
                 1 
                 0 
                 1 
               
               
                 PC032 
                 N/A 
                 3 + 3 
                 T3b 
                 N0 
                 M0 
                 11.5 
                 0 
                 0 
                 0 
                 0 
               
               
                 PC215 
                 62 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 12.3 
                 0 
                 0 
                 0 
                 0 
               
               
                 PC092 
                 68 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 13.7 
                 0 
                 0 
                 0 
                 0 
               
               
                 PC102 
                 48 
                 3 + 3 
                 T2b 
                 N1 
                 M0 
                 16 
                 0 
                 1 
                 0 
                 1 
               
               
                 PC037 
                 50 
                 4 + 3 
                 T2b 
                 N0 
                 M0 
                 16.2 
                 0 
                 0 
                 0 
                 0 
               
               
                 PC195 
                 55 
                 3 + 4 
                 T2b 
                 N0 
                 M0 
                 5.8 
                 0 
                 0 
                 0 
                 0 
               
               
                 PC190 
                 72 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 6.5 
                 0 
                 0 
                 0 
                 0 
               
               
                 PC021 
                 61 
                 3 + 3 
                 T2b 
                 N0 
                 M0 
                 9.8 
                 0 
                 0 
                 0 
                 0 
               
               
                 PC005 
                 N/A 
                 3 + 3 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 1 
                 0 
                 0 
               
               
                 PC177 
                 57 
                 3 + 4 
                 T2a 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 0 
                 0 
                 0 
               
               
                 PC233 
                 N/A 
                 3 + 3 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 N/A 
                 0 
                 0 
                 0 
               
               
                 PC313 
                 50 
                 3 + 4 
                 T2 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 0 
                 0 
                 0 
               
               
                 PC056 
                 68 
                 3 + 4 
                 T2b 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 0 
                 0 
                 0 
               
               
                 PC173 
                 72 
                 3 + 3 
                 T3b 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 0 
                 0 
                 0 
               
               
                 PC110 
                 48 
                 4 + 4 
                 T2b 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 0 
                 0 
                 0 
               
               
                 PC153 
                 64 
                 adenoid 
                 T2b 
                 N0 
                 M0 
                 N/A 
                 N/A 
                 0 
                 0 
                 0 
               
               
                   
                   
                 cystic 
               
               
                 PC318 
                 56 
                 4 + 3 
                 T3a 
                 N0 
                 Mx 
                 N/A 
                 N/A 
                 0 
                 0 
                 0 
               
               
                   
               
               
                 LN meta: lymph node metastasis. N/A: non available. 
               
               
                 (a) All patients hade one tumor sample analyzed. A fraction of patients hade also normal tissues from unaffected areas of the prostate analyzed; they are presented as the “normal” cluster in FIG. 2. 
               
               
                 (b) Increasing the q value in the one-class SAM (significant analysis of microarrays) ranking test gave a list of increased number of significant ES genes as shown in FIG. 1. By choosing different q value cut-off at 0.01, 0.05 and 0.1, there were 201, 641 and 1386 significant ES genes selected respectively. Using the expression profile of these three gene lists to predict the tumor aggressiveness gave some slight different results as shown in this table. The result by the gene list at q ≦ 0.05 gave the best prediction. 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Lung adenocarcinoma clinical data and ES type 
               
             
          
           
               
                 Clinical and pathological data, Garber et al., 2001 
                   
               
               
                 (Ref. # 63) 
                 This invention 
               
             
          
           
               
                   
                 Survival 
                   
                 ES type (b) 
               
             
          
           
               
                 Patient (a) 
                 Grade 
                 Stage 
                 (months) 
                 Status 
                 q ≦ 0.01 
                 q ≦ 0.05 
                 q ≦ 0.1 
               
               
                   
               
               
                 313-99 
                 3 
                 pT2pN1pM1 
                 17 
                 1 
                 0 
                 0 
                 0 
               
               
                 198-96 
                 2 
                 pT1pN2 
                  1 
                 1 
                 0 
                 0 
                 0 
               
               
                 199-97 
                 2 
                 pT2pN1pM1 
                 16 
                 1 
                 0 
                 0 
                 0 
               
               
                 218-97 
                 3 
                 pT2pN2 
                 12 
                 1 
                 0 
                 0 
                 1 
               
               
                 181-96 
                 2 
                 pT4pN0 M1 
                 25 
                 1 
                 0 
                 0 
                 1 
               
               
                 204-97 
                 2 
                 pT2pN2 M1 
                 36 
                 1 
                 1 
                 0 
                 1 
               
               
                 165-96 
                 2 
                 pT1pN2 M1 
                   18+ 
                 0 
                 0 
                 0 
                 0 
               
               
                 222-97 
                 3 
                 pT2pN2 
                   48+ 
                 0 
                 0 
                 0 
                 0 
               
               
                 226-97 
                 3 
                 pT3pN2 
                   48+ 
                 0 
                 0 
                 0 
                 0 
               
               
                 137-96 
                 2 
                 pT2pN0 
                 32 
                 0 
                 0 
                 0 
                 0 
               
               
                 156-96 
                 1 
                 pT2pN0 
                   54+ 
                 0 
                 0 
                 0 
                 0 
               
               
                 180-96 
                 2 
                 pT1pN0 
                   54+ 
                 0 
                 0 
                 0 
                 0 
               
               
                 187-96 
                 2 
                 pT1pN0 
                   54+ 
                 0 
                 0 
                 0 
                 0 
               
               
                 185-96 
                 2 
                 pT1pN0 M0 
                   54+ 
                 0 
                 0 
                 0 
                 0 
               
               
                 132-95 
                 3 
                 pT1pN0 
                 37 
                 0 
                 0 
                 0 
                 1 
               
               
                 320-00 
                 3 
                 pT2pN1pM1 
                   
                   
                 0 
                 0 
                 0 
               
               
                  68-96 
                 2 
                 pT1pN0 
                   
                   
                 0 
                 0 
                 0 
               
               
                 319-00PT 
                 2 
                 pT1pN2pM1 
                   
                   
                 0 
                 0 
                 1 
               
               
                 Nov-00 
                 2 
                 pT2pN0 
                   
                   
                 1 
                 0 
                 1 
               
               
                 Dec-00 
                 2 
                 pT1pN1 
                   
                   
                 0 
                 0 
                 1 
               
               
                 223-97 
                 3 
                 pT2pN2 
                  5 
                 1 
                 1 
                 1 
                 0 
               
               
                 257-97 
                 3 
                 pT2pN2 
                  2 
                 1 
                 0 
                 1 
                 1 
               
               
                  59-96 
                 3 
                 pT2pN0 M1 
                 11 
                 1 
                 1 
                 1 
                 1 
               
               
                  80-96 
                 3 
                 pT2pN2 M1 
                  3 
                 1 
                 1 
                 1 
                 1 
               
               
                 139-96 
                 3 
                 pT3pN1pM1 
                  5 
                 1 
                 1 
                 1 
                 1 
               
               
                 184-96 
                 2 
                 pT2pN2 M1 
                  3 
                 1 
                 1 
                 1 
                 1 
               
               
                 234-97 
                 3 
                 pT2pN2pM1 
                  0 
                 1 
                 1 
                 1 
                 1 
               
               
                 265-98 
                 2 
                 pT1 
                 15 
                 1 
                 1 
                 1 
                 1 
               
               
                 306-99 
                 3 
                 pT2pN1 
                   24+ 
                 0 
                 1 
                 1 
                 1 
               
               
                 319-00MT 
                 3 
                   
                   
                   
                 0 
                 1 
                 0 
               
               
                 178-96 
                 2 
                 pT2pN0 
                   
                   
                 1 
                 1 
                 1 
               
               
                   
               
               
                 (a) Table 3 presents clinical data from lung adenocarcinoma cases only. In FIG. 3 cases with non-adenocarcinoma are included, comprising large cell lung cancer, small cell lung cancer, and squamous cell lung cancer. The non-adenocarcinoma cases were analyzed by gene expression profiling in the original publication but lacked clinical follow-up data. 
               
               
                 (b) By choosing different q value cut-off at 0.01, 0.05 and 0.1, 201, 641, and 1386, respectively, significant ES genes were selected. Using the expression profile of the corresponding gene lists for tumor aggressiveness prediction provided slightly different results as shown Table 3. The q ≦ 0.05 gene list gave the best prediction. 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Gastric cancer clinical data and ES type 
               
             
          
           
               
                 Clinical and pathological data, Chen et al., 2003 (Ref. # 64) 
                 This 
               
             
          
           
               
                 Sample 
                   
                 Tumor 
                   
                 Tumor 
                   
                 EBV 
                 Survival 
                 Survival, 
                 invention 
               
               
                 ID (a) 
                 SEX 
                 site 
                 Tumor type 
                 stage 
                 
                   H. pylori 
                 
                 ISH 
                 status 
                 months 
                 ES type (b) 
               
               
                   
               
             
          
           
               
                 HKG11T 
                 F 
                 Antrum 
                 Diffused 
                 IVA 
                 − 
                 − 
                 1 
                 2 
                 1 
               
               
                 HKG38T 
                 F 
                 Cardia 
                 Intestinal 
                 IVA 
                 − 
                 − 
                 1 
                 3 
                 1 
               
               
                 HKG23T 
                 M 
                 Antrum 
                 Intestinal 
                 IVB 
                 − 
                 − 
                 1 
                 3 
                 1 
               
               
                 HKG68T 
                 M 
                 Cardia 
                 Intestinal 
                 IVB 
                 + 
                 − 
                 1 
                 3 
                 1 
               
               
                 HKG1T 
                 F 
                 Antrum 
                 Diffused 
                 IIIA 
                 − 
                 − 
                 1 
                 4 
                 1 
               
               
                 HKG55T 
                 M 
                 Antrum 
                 Diffused 
                 IIIB 
                 − 
                 − 
                 1 
                 4 
                 1 
               
               
                 HKG69T 
                 F 
                 Cardia 
                 Intestinal 
                 IIIB 
                 − 
                 − 
                 1 
                 4 
                 1 
               
               
                 HKG49T 
                 F 
                 Cardia 
                 Mixed 
                 IVA 
                 + 
                 − 
                 1 
                 4 
                 1 
               
               
                 HKG27T 
                 F 
                 Cardia 
                 Intestinal 
                 IIIB 
                 − 
                 − 
                 1 
                 5 
                 1 
               
               
                 HKG64T 
                 M 
                 Antrum 
                 Intestinal 
                 IIIA 
                 + 
                 − 
                 1 
                 6 
                 1 
               
               
                 HKG32T 
                 F 
                 Antrum 
                 Intestinal 
                 II 
                 − 
                 − 
                 1 
                 8 
                 1 
               
               
                 HKG53T 
                 M 
                 Cardia 
                 Mixed 
                 IVA 
                 + 
                 − 
                 1 
                 8 
                 1 
               
               
                 HKG2T 
                 M 
                 Antrum 
                 Intestinal 
                 IIIB 
                 + 
                 − 
                 1 
                 10 
                 1 
               
               
                 HKG31T 
                 M 
                 Cardia 
                 Intestinal 
                 IVA 
                 − 
                 − 
                 1 
                 10 
                 1 
               
               
                 HKG78T 
                 M 
                 Cardia 
                 Mixed 
                 IIIB 
                 + 
                 − 
                 1 
                 10 
                 1 
               
               
                 HKG42T 
                 M 
                 Body 
                 Intestinal 
                 IIIA 
                 − 
                 + 
                 1 
                 12 
                 1 
               
               
                 HKG30T 
                 F 
                 Body 
                 Intestinal 
                 IIIB 
                 − 
                 − 
                 1 
                 12 
                 1 
               
               
                 HKG44T 
                 F 
                 Antrum 
                 Diffused 
                 IIIA 
                 + 
                 − 
                 1 
                 14 
                 1 
               
               
                 HKG36T 
                 M 
                 Body 
                 Intestinal 
                 IIIA 
                 + 
                 − 
                 1 
                 15 
                 1 
               
               
                 HKG19T 
                 M 
                 Cardia 
                 Intestinal 
                 IVA 
                 + 
                 − 
                 1 
                 20 
                 1 
               
               
                 HKG34T 
                 M 
                 Cardia 
                 Intestinal 
                 IVA 
                 + 
                 − 
                 1 
                 20 
                 1 
               
               
                 HKG51T 
                 F 
                 Body 
                 Mixed 
                 IIIA 
                 + 
                 − 
                 1 
                 21 
                 1 
               
               
                 HKG6T 
                 M 
                 Antrum 
                 Diffused 
                 IIIA 
                 + 
                 − 
                 1 
                 26 
                 1 
               
               
                 HKG52T 
                 F 
                 Antrum 
                 Diffused 
                 IIIB 
                 + 
                 − 
                 1 
                 27 
                 1 
               
               
                 HKG9T 
                 M 
                 Cardia 
                 Intestinal 
                 IIIB 
                 − 
                 − 
                 1 
                 27 
                 1 
               
               
                 HKG8T 
                 M 
                 Body 
                 Intestinal 
                 IIIA 
                 + 
                 − 
                 1 
                 29 
                 1 
               
               
                 HKG35T 
                 F 
                 Antrum 
                 Diffused 
                 IIIA 
                 − 
                 − 
                 1 
                 30 
                 1 
               
               
                 HKG73T 
                 M 
                 Body 
                 Intestinal 
                 II 
                 + 
                 + 
                 1 
                 32 
                 1 
               
               
                 HKG61T 
                 M 
                 Body 
                 Intestinal 
                 IIIA 
                 + 
                 − 
                 1 
                 38 
                 1 
               
               
                 HKG87T 
                 F 
                 Antrum 
                 Diffused 
                 IIIA 
                 − 
                 − 
                 1 
                 45 
                 1 
               
               
                 HKG20T 
                 M 
                 Antrum 
                 Diffused 
                 IIIB 
                 + 
                 − 
                 1 
                 45 
                 1 
               
               
                 HKG18T 
                 F 
                 Antrum 
                 Intestinal 
                 II 
                 + 
                 − 
                 0 
                 1 
                 1 
               
               
                 HKG84T 
                 F 
                 Antrum 
                 Intestinal 
                 IIIA 
                 + 
                 − 
                 0 
                 1 
                 1 
               
               
                 HKG26T 
                 M 
                 Cardia 
                 Intestinal 
                 IIIB 
                 + 
                 + 
                 0 
                 1 
                 1 
               
               
                 HKG92T 
                 M 
                 Cardia 
                 Intestinal 
                 IB 
                 − 
                 − 
                 0 
                 11 
                 1 
               
               
                 HKG71T 
                 M 
                 Antrum 
                 Diffused 
                 IIIB 
                 − 
                 − 
                 0 
                 16 
                 1 
               
               
                 HKG90T 
                 M 
                 Antrum 
                 Intestinal 
                 IB 
                 + 
                 − 
                 0 
                 18 
                 1 
               
               
                 HKG76T 
                 M 
                 Cardia 
                 Intestinal 
                 IB 
                 − 
                 − 
                 0 
                 27 
                 1 
               
               
                 HKG74T 
                 F 
                 Body 
                 Intestinal 
                 IB 
                 + 
                 − 
                 0 
                 28 
                 1 
               
               
                 HKG77T 
                 F 
                 Antrum 
                 Intestinal 
                 II 
                 + 
                 − 
                 0 
                 29 
                 1 
               
               
                 HKG43T 
                 F 
                 Cardia 
                 Intestinal 
                 II 
                 − 
                 − 
                 0 
                 32 
                 1 
               
               
                 HKG70T 
                 M 
                 Antrum 
                 Intestinal 
                 II 
                 + 
                 − 
                 0 
                 34 
                 1 
               
               
                 HKG67T 
                 M 
                 Antrum 
                 Intestinal 
                 IIIA 
                 + 
                 − 
                 0 
                 37 
                 1 
               
               
                 HKG66T 
                 M 
                 Antrum 
                 Intestinal 
                 II 
                 − 
                 − 
                 0 
                 38 
                 1 
               
               
                 HKG63T 
                 F 
                 Antrum 
                 Intestinal 
                 II 
                 + 
                 − 
                 0 
                 42 
                 1 
               
               
                 HKG3T 
                 M 
                 Antrum 
                 Intestinal 
                 IB 
                 + 
                 − 
                 0 
                 45 
                 1 
               
               
                 HKG58T 
                 M 
                 Antrum 
                 Intestinal 
                 II 
                 + 
                 − 
                 0 
                 46 
                 1 
               
               
                 HKG22T 
                 F 
                 Cardia 
                 Mixed 
                 IB 
                 − 
                 − 
                 0 
                 51 
                 1 
               
               
                 HKG33T 
                 M 
                 Antrum 
                 Mixed 
                 IIIA 
                 − 
                 − 
                 0 
                 51 
                 1 
               
               
                 HKG15T 
                 F 
                 Antrum 
                 Mixed 
                 IB 
                 + 
                 − 
                 0 
                 57 
                 1 
               
               
                 HKG13T 
                 M 
                 Antrum 
                 Intestinal 
                 II 
                 − 
                 − 
                 0 
                 91 
                 1 
               
               
                 HKG29T 
                 F 
                 Body 
                 Intestinal 
                 IIIA 
                 − 
                 − 
                 N/A 
                 N/A 
                 0b 
               
               
                 HKG57T 
                 M 
                 Antrum 
                 Diffused 
                 IVA 
                 − 
                 − 
                 1 
                 2 
                 0a 
               
               
                 HKG21T 
                 M 
                 Body 
                 Intestinal 
                 IIIA 
                 + 
                 + 
                 1 
                 5 
                 0b 
               
               
                 HKG5T 
                 M 
                 Cardia 
                 Intestinal 
                 IIIB 
                 − 
                 − 
                 1 
                 6 
                 0a 
               
               
                 HKG25T 
                 M 
                 Cardia 
                 Intestinal 
                 IVB 
                 − 
                 − 
                 1 
                 8 
                 0b 
               
               
                 HKG60T 
                 M 
                 Body 
                 Intestinal 
                 IVA 
                 + 
                 + 
                 1 
                 10 
                 0b 
               
               
                 HKG41T 
                 F 
                 Antrum 
                 Intestinal 
                 IIIA 
                 − 
                 − 
                 1 
                 13 
                 0a 
               
               
                 HKG39T 
                 F 
                 Cardia 
                 Intestinal 
                 IIIA 
                 + 
                 − 
                 1 
                 14 
                 0a 
               
               
                 HKG89T 
                 M 
                 Cardia 
                 Intestinal 
                 IVB 
                 + 
                 + 
                 1 
                 15 
                 0b 
               
               
                 HKG16T 
                 M 
                 Antrum 
                 Intestinal 
                 IIIA 
                 − 
                 − 
                 1 
                 16 
                 0a 
               
               
                 HKG82T 
                 F 
                 Antrum 
                 Intestinal 
                 IIIB 
                 + 
                 − 
                 1 
                 17 
                 0a 
               
               
                 HKG48T 
                 F 
                 Cardia 
                 Intestinal 
                 IVA 
                 − 
                 − 
                 1 
                 18 
                 0a 
               
               
                 HKG17T 
                 F 
                 Diffused 
                 Diffused 
                 IIIB 
                 − 
                 − 
                 1 
                 20 
                 0b 
               
               
                 HKG24T 
                 F 
                 Antrum 
                 indeterminate 
                 IIIA 
                 + 
                 − 
                 1 
                 20 
                 0a 
               
               
                 HKG37T 
                 M 
                 Cardia 
                 Intestinal 
                 IB 
                 − 
                 − 
                 1 
                 43 
                 0a 
               
               
                 HKG79T 
                 F 
                 Antrum 
                 Intestinal 
                 IB 
                 − 
                 − 
                 0 
                 1 
                 0a 
               
               
                 HKG45T 
                 M 
                 Body 
                 Intestinal 
                 IIIB 
                 + 
                 + 
                 0 
                 1 
                 0b 
               
               
                 HKG47T 
                 M 
                 Cardia 
                 Intestinal 
                 IIIB 
                 − 
                 − 
                 0 
                 2 
                 0b 
               
               
                 HKG10T 
                 F 
                 Body 
                 Intestinal 
                 IIIB 
                 + 
                 + 
                 0 
                 3 
                 0b 
               
               
                 HKG94T 
                 M 
                 Body 
                 Intestinal 
                 II 
                 − 
                 + 
                 0 
                 9 
                 0b 
               
               
                 HKG93T 
                 F 
                 Body 
                 Intestinal 
                 IB 
                 + 
                 + 
                 0 
                 11 
                 0b 
               
               
                 HKG81T 
                 F 
                 Antrum 
                 Intestinal 
                 II 
                 − 
                 − 
                 0 
                 12 
                 0a 
               
               
                 HKG91T 
                 M 
                 Cardia 
                 Intestinal 
                 IB 
                 + 
                 − 
                 0 
                 18 
                 0b 
               
               
                 HKG75T 
                 F 
                 Cardia 
                 Intestinal 
                 II 
                 − 
                 − 
                 0 
                 21 
                 0a 
               
               
                 HKG83T 
                 F 
                 Antrum 
                 Intestinal 
                 II 
                 − 
                 − 
                 0 
                 21 
                 0a 
               
               
                 HKG28T 
                 M 
                 Cardia 
                 Intestinal 
                 IIIA 
                 − 
                 − 
                 0 
                 22 
                 0a 
               
               
                 HKG72T 
                 F 
                 Antrum 
                 Intestinal 
                 II 
                 + 
                 − 
                 0 
                 31 
                 0a 
               
               
                 HKG80T 
                 M 
                 Antrum 
                 Intestinal 
                 II 
                 + 
                 − 
                 0 
                 32 
                 0a 
               
               
                 HKG65T 
                 F 
                 Antrum 
                 Diffused 
                 IIIA 
                 + 
                 − 
                 0 
                 38 
                 0b 
               
               
                 HKG59T 
                 M 
                 Antrum 
                 Intestinal 
                 II 
                 + 
                 − 
                 0 
                 41 
                 0a 
               
               
                 HKG40T 
                 F 
                 Body 
                 Intestinal 
                 II 
                 − 
                 − 
                 0 
                 43 
                 0a 
               
               
                 HKG62T 
                 F 
                 Antrum 
                 Intestinal 
                 IVA 
                 + 
                 − 
                 0 
                 44 
                 0a 
               
               
                 HKG54T 
                 M 
                 Cardia 
                 Intestinal 
                 IIIA 
                 − 
                 + 
                 0 
                 49 
                 0b 
               
               
                 HKG56T 
                 M 
                 Body 
                 Intestinal 
                 IIIA 
                 + 
                 + 
                 0 
                 49 
                 0b 
               
               
                 HKG7T 
                 F 
                 Body 
                 Mixed 
                 IIIA 
                 + 
                 − 
                 0 
                 51 
                 0b 
               
               
                 HKG14T 
                 M 
                 Body 
                 Intestinal 
                 IB 
                 + 
                 − 
                 0 
                 71 
                 0a 
               
               
                 HKG46T 
                 M 
                 Body 
                 Intestinal 
                 IA 
                 + 
                 − 
                 0 
                 77 
                 0b 
               
               
                 HKG12T 
                 M 
                 Antrum 
                 Intestinal 
                 IIIB 
                 − 
                 − 
                 0 
                 87 
                 0a 
               
               
                   
               
               
                 (a) Only tumor sample ID was indicated in Table 4. Some cases had both a tumor sample and a normal sample from respective stomach areas analyzed by gene expression profiling. The normal samples formed a normal cluster as shown in FIG. 5. 
               
               
                 (b) The ES type was determined by using the gene list of 641 ES predictor genes selected at q ≦ 0.05 in the one-class SAM. 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Leukemia clinical data and ES type 
               
             
          
           
               
                 Clinical data, Bullinger et al., 2004 (Ref. # 66) 
                 This 
               
             
          
           
               
                   
                   
                   
                 Overall 
                 invention 
               
               
                 Sample ID 
                 Cytogenetic group 
                 Status 
                 survival (days) 
                 ES type (a) 
               
               
                   
               
             
          
           
               
                 AML 26 
                 t(8; 21) 
                 alive 
                 138 
                 1 
               
               
                 AML 71 
                 other 
                 alive 
                 138 
                 1 
               
               
                 AML 49 
                 normal karyotype 
                 alive 
                 211 
                 1 
               
               
                 AML 105 
                 t(8; 21) 
                 alive 
                 211 
                 1 
               
               
                 AML 75 
                 normal karyotype 
                 alive 
                 238 
                 1 
               
               
                 AML 47 
                 del(7q)/-7 
                 alive 
                 281 
                 1 
               
               
                 AML 94 
                 normal karyotype 
                 alive 
                 359 
                 1 
               
               
                 AML 44 
                 t(8; 21) 
                 alive 
                 509 
                 1 
               
               
                 AML 30 
                 normal karyotype 
                 alive 
                 515 
                 1 
               
               
                 AML 16 
                 t(8; 21) 
                 alive 
                 610 
                 1 
               
               
                 AML 114 
                 t(8; 21) 
                 alive 
                 611 
                 1 
               
               
                 AML 51 
                 del(7q)/-7 
                 alive 
                 622 
                 1 
               
               
                 AML 48 
                 t(8; 21) 
                 alive 
                 836 
                 1 
               
               
                 AML 115 
                 normal karyotype 
                 alive 
                 1107 
                 1 
               
               
                 AML 107 
                 +8sole 
                 dead 
                 7 
                 1 
               
               
                 AML 58 
                 del(7q)/-7 
                 dead 
                 12 
                 1 
               
               
                 AML 98 
                 t(8; 21) 
                 dead 
                 15 
                 1 
               
               
                 AML 78 
                 complex karyotype 
                 dead 
                 21 
                 1 
               
               
                 AML 42 
                 normal karyotype 
                 dead 
                 31 
                 1 
               
               
                 AML 57 
                 normal karyotype 
                 dead 
                 32 
                 1 
               
               
                 AML 52 
                 del(7q)/-7 
                 dead 
                 33 
                 1 
               
               
                 AML 24 
                 complex karyotype 
                 dead 
                 35 
                 1 
               
               
                 AML 92 
                 del(7q)/-7 
                 dead 
                 44 
                 1 
               
               
                 AML 56 
                 normal karyotype 
                 dead 
                 75 
                 1 
               
               
                 AML 13 
                 normal karyotype 
                 dead 
                 85 
                 1 
               
               
                 AML 118 
                 normal karyotype 
                 dead 
                 99 
                 1 
               
               
                 AML 102 
                 normal karyotype 
                 dead 
                 102 
                 1 
               
               
                 AML 62 
                 t(8; 21) 
                 dead 
                 126 
                 1 
               
               
                 AML 113 
                 normal karyotype 
                 dead 
                 142 
                 1 
               
               
                 AML 39 
                 normal karyotype 
                 dead 
                 146 
                 1 
               
               
                 AML 61 
                 normal karyotype 
                 dead 
                 182 
                 1 
               
               
                 AML 93 
                 normal karyotype 
                 dead 
                 203 
                 1 
               
               
                 AML 4 
                 t(8; 21) 
                 dead 
                 210 
                 1 
               
               
                 AML 5 
                 complex karyotype 
                 dead 
                 243 
                 1 
               
               
                 AML 76 
                 normal karyotype 
                 dead 
                 250 
                 1 
               
               
                 AML 96 
                 normal karyotype 
                 dead 
                 273 
                 1 
               
               
                 AML 45 
                 normal karyotype 
                 dead 
                 291 
                 1 
               
               
                 AML 87 
                 normal karyotype 
                 dead 
                 316 
                 1 
               
               
                 AML 18 
                 other 
                 dead 
                 323 
                 1 
               
               
                 AML 80 
                 del(7q)/-7 
                 dead 
                 333 
                 1 
               
               
                 AML 67 
                 +8sole 
                 dead 
                 414 
                 1 
               
               
                 AML 66 
                 del(7q)/-7 
                 dead 
                 470 
                 1 
               
               
                 AML 41 
                 other 
                 dead 
                 540 
                 1 
               
               
                 AML 17 
                 normal karyotype 
                 dead 
                 570 
                 1 
               
               
                 AML 46 
                 normal karyotype 
                 dead 
                 663 
                 1 
               
               
                 AML 108 
                 normal karyotype 
                 dead 
                 672 
                 1 
               
               
                 AML 14 
                 del(7q)/-7 
                 dead 
                 711 
                 1 
               
               
                 AML 8 
                 normal karyotype 
                 alive 
                 206 
                 0a 
               
               
                 AML 116 
                 normal karyotype 
                 alive 
                 271 
                 0a 
               
               
                 AML 72 
                 complex karyotype 
                 alive 
                 297 
                 0a 
               
               
                 AML 25 
                 inv(16) 
                 alive 
                 400 
                 0a 
               
               
                 AML 34 
                 inv(16) 
                 alive 
                 422 
                 0a 
               
               
                 AML 9 
                 normal karyotype 
                 alive 
                 438 
                 0a 
               
               
                 AML 53 
                 inv(16) 
                 alive 
                 493 
                 0a 
               
               
                 AML 84 
                 inv(16) 
                 alive 
                 511 
                 0a 
               
               
                 AML 112 
                 normal karyotype 
                 alive 
                 524 
                 0a 
               
               
                 AML 70 
                 inv(16) 
                 alive 
                 551 
                 0a 
               
               
                 AML 89 
                 inv(16) 
                 alive 
                 609 
                 0a 
               
               
                 AML 12 
                 normal karyotype 
                 alive 
                 610 
                 0a 
               
               
                 AML 55 
                 normal karyotype 
                 alive 
                 688 
                 0a 
               
               
                 AML 35 
                 normal karyotype 
                 alive 
                 689 
                 0a 
               
               
                 AML 90 
                 inv(16) 
                 alive 
                 690 
                 0a 
               
               
                 AML 109 
                 normal karyotype 
                 alive 
                 720 
                 0a 
               
               
                 AML 81 
                 inv(16) 
                 alive 
                 839 
                 0a 
               
               
                 AML 20 
                 t(9; 11) 
                 alive 
                 884 
                 0a 
               
               
                 AML 65 
                 inv(16) 
                 alive 
                 980 
                 0a 
               
               
                 AML 43 
                 normal karyotype 
                 alive 
                 987 
                 0a 
               
               
                 AML 50 
                 t(9; 11) 
                 alive 
                 1296 
                 0a 
               
               
                 AML 79 
                 inv(16) 
                 alive 
                 1388 
                 0a 
               
               
                 AML 97 
                 inv(16) 
                 alive 
                 1625 
                 0a 
               
               
                 AML 23 
                 t(8; 21) 
                 dead 
                 28 
                 0a 
               
               
                 AML 77 
                 inv(16) 
                 dead 
                 44 
                 0a 
               
               
                 AML 28 
                 normal karyotype 
                 dead 
                 78 
                 0a 
               
               
                 AML 91 
                 normal karyotype 
                 dead 
                 94 
                 0a 
               
               
                 AML 64 
                 normal karyotype 
                 dead 
                 96 
                 0a 
               
               
                 AML 7 
                 normal karyotype 
                 dead 
                 134 
                 0a 
               
               
                 AML 22 
                 normal karyotype 
                 dead 
                 154 
                 0a 
               
               
                 AML 73 
                 inv(16) 
                 dead 
                 177 
                 0a 
               
               
                 AML 11 
                 normal karyotype 
                 dead 
                 204 
                 0a 
               
               
                 AML 40 
                 normal karyotype 
                 dead 
                 215 
                 0a 
               
               
                 AML 111 
                 t(9; 11) 
                 dead 
                 278 
                 0a 
               
               
                 AML 110 
                 normal karyotype 
                 dead 
                 318 
                 0a 
               
               
                 AML 27 
                 normal karyotype 
                 dead 
                 326 
                 0a 
               
               
                 AML 38 
                 t(8; 21) 
                 dead 
                 334 
                 0a 
               
               
                 AML 88 
                 t(9; 11) 
                 dead 
                 335 
                 0a 
               
               
                 AML 31 
                 +8sole 
                 dead 
                 336 
                 0a 
               
               
                 AML 54 
                 other 
                 dead 
                 346 
                 0a 
               
               
                 AML 36 
                 normal karyotype 
                 dead 
                 374 
                 0a 
               
               
                 AML 37 
                 t(15; 17) 
                 dead 
                 400 
                 0a 
               
               
                 AML 103 
                 inv(16) 
                 dead 
                 429 
                 0a 
               
               
                 AML 15 
                 normal karyotype 
                 dead 
                 483 
                 0a 
               
               
                 AML 74 
                 normal karyotype 
                 dead 
                 511 
                 0a 
               
               
                 AML 85 
                 normal karyotype 
                 dead 
                 1220 
                 0a 
               
               
                 AML 95 
                 t(15; 17) 
                 alive 
                 365 
                 0b 
               
               
                 AML 99 
                 t(15; 17) 
                 alive 
                 521 
                 0b 
               
               
                 AML 59 
                 other 
                 alive 
                 724 
                 0b 
               
               
                 AML 83 
                 t(9; 11) 
                 alive 
                 744 
                 0b 
               
               
                 AML 69 
                 t(9; 11) 
                 alive 
                 748 
                 0b 
               
               
                 AML 2 
                 t(15; 17) 
                 alive 
                 801 
                 0b 
               
               
                 AML 33 
                 t(15; 17) 
                 alive 
                 836 
                 0b 
               
               
                 AML 68 
                 t(9; 11) 
                 alive 
                 1053 
                 0b 
               
               
                 AML 86 
                 t(15; 17) 
                 alive 
                 1212 
                 0b 
               
               
                 AML 101 
                 t(15; 17) 
                 alive 
                 1352 
                 0b 
               
               
                 AML 119 
                 t(15; 17) 
                 dead 
                 0 
                 0b 
               
               
                 AML 32 
                 +8sole 
                 dead 
                 1 
                 0b 
               
               
                 AML 117 
                 t(15; 17) 
                 dead 
                 1 
                 0b 
               
               
                 AML 104 
                 t(15; 17) 
                 dead 
                 3 
                 0b 
               
               
                 AML 21 
                 t(9; 11) 
                 dead 
                 21 
                 0b 
               
               
                 AML 106 
                 del(7q)/-7 
                 dead 
                 139 
                 0b 
               
               
                 AML 1 
                 complex karyotype 
                 dead 
                 213 
                 0b 
               
               
                 AML 10 
                 normal karyotype 
                 dead 
                 233 
                 0b 
               
               
                 AML 63 
                 del(7q)/-7 
                 dead 
                 281 
                 0b 
               
               
                 AML 60 
                 t(15; 17) 
                 dead 
                 299 
                 0b 
               
               
                 AML 6 
                 del(7q)/-7 
                 dead 
                 336 
                 0b 
               
               
                 AML 29 
                 t(15; 17) 
                 dead 
                 730 
                 0b 
               
               
                   
               
               
                 (a) The ES type was determined by using the gene list of 641 ES predictor genes selected at q ≦ 0.05 in the one-class SAM. 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 Abbreviations 
               
             
          
           
               
                 Abbreviation 
                 Full term 
               
               
                   
               
               
                 ES 
                 embryonic stem 
               
               
                 RNASEL 
                 ribonuclease L (2′,5′-oligoisoadenylate 
               
               
                 (HPC1) 
                 synthetase-dependent)/hereditary prostate cancer 1 
               
               
                 ELAC2/HPC2 
                 elaC homolog 2 ( E. coli )/hereditary prostate 
               
               
                   
                 cancer 2 
               
               
                 GSTP1 
                 glutathione S-transferase pi 
               
               
                 AMACR 
                 alpha-methylacyl-CoA racemase 
               
               
                 HPN 
                 hepsin 
               
               
                 PIM1 
                 pim-1 oncogene 
               
               
                 EZH2 
                 enhancer of zeste homolog 2 
               
               
                 AZGP1 
                 alpha-2-glycoprotein 1, zinc 
               
               
                 MUC1 
                 mucin 1, cell surface associated 
               
               
                 SMD 
                 Stanford Microarray Database 
               
               
                 RNA 
                 ribonuclear acid 
               
               
                 DNA 
                 dioxyribonuclear acid 
               
               
                 cDNA 
                 complementary dioxyribonuclear acid 
               
               
                 SUID 
                 Stanford Unique Identification Number 
               
               
                 UID 
                 unique Identification Number 
               
               
                 R/G 
                 red channel/green channel 
               
               
                 GO 
                 gene ontology 
               
               
                 IMAGE 
                 the Integrated Molecular Analysis of Genomes 
               
               
                   
                 and their Expression 
               
               
                 PSA 
                 prostate specific antigen 
               
               
                 RR 
                 relative risk 
               
               
                 SE 
                 standard error 
               
               
                 EBV 
                 Epstein-Barr virus 
               
               
                 ISH 
                 in situ hybridization 
               
               
                 AML 
                 acute myeloid leukemia 
               
               
                 
                   H. pylori 
                 
                 
                   Helicobacter pylori 
                 
               
               
                 SAM 
                 significant analysis of microarrays 
               
               
                 TF 
                 transcriptional factor 
               
               
                 t(15; 17) 
                 translocation between chromosome 15 and 
               
               
                   
                 chromosome 17 
               
               
                 del(7q) 
                 deletion of the long arm of chromosome 7 
               
               
                 inv(16) 
                 inversion of chromosome 16 
               
               
                 AML 
                 acute myeloid leukemia. 
               
               
                 NA 
                 not available. 
               
               
                 t(15; 17) 
                 translocation between chromosome 15 and 
               
               
                   
                 chromosome 17 
               
               
                 del(7q) 
                 deletion of the long arm of chromosome 7 
               
               
                 inv(16) 
                 inversion of chromosome 16 
               
               
                 F 
                 female 
               
               
                 M 
                 male 
               
               
                   
               
               
                 Note: 
               
               
                 The gene symbols for all genes in this invention are given according to their standard symbol in the National Center for Biotechnology Information&#39;s gene database (http://www.ncbi.nlm.nih.gov/entrez/querv.fcgi?db=gene&amp;cmd=search&amp;term). For expressed sequence tag (EST) without gene symbol, the IMAGE clone ID or the UniGene cluster ID are given