Marker genes for prostate cancer classification

Abstract

The present invention relates to a method for classifying a prostate cancer in a subject, the method comprising the steps of a) determining a gene expression level or gene expression pattern of the genes F3 and IGFBP3 in a sample from the subject and b) classifying the tumor by comparing the gene expression level determined in a) with a reference gene expression of the same genes in reference patients known to have a high risk or low risk tumor respectively. In addition the invention relates to a method for determining prognosis of a subject diagnosed with prostate cancer, a method for making a treatment decision for a subject diagnosed with prostate cancer and a solid support or a kit for classifying a tumor in a subject diagnosed with prostate cancer.

1 .- 25 . (canceled) 
     
     
         26 . A method diagnosing and treating a low or high risk tumor in a subject with prostate cancer, the method comprising:
 a. obtaining a sample from a subject with prostate cancer:   b. detecting expression levels of genes F3 and IGFBP3 in the sample and determining whether the expression levels of genes F3 and IGFBP3 are higher or lower compared to expression levels of F3 and IGFBP3 from a reference sample;   c. diagnosing the subject with a low risk tumor when the expression levels of genes F3 and IGFBP3 in the sample are higher compared to expression levels of genes F3 and IGFBP3 from a reference sample or diagnosing the subject with a high risk tumor when the expression levels of genes F3 and IGFBP3 in the sample are lower compared to expression levels of genes F3 and IGFBP3 from a reference sample; and   d. withholding prostatectomy, radiation, chemotherapy, castration, anti-androgen therapy or a combination thereof from the subject with a low risk tumor or administering a lower dose of radiation, chemotherapy anti-androgen therapy or a combination thereof to the subject with a low risk tumor or administering treatment of prostatectomy, radiation, chemotherapy, castration or a combination thereof to the subject with a high risk tumor.   
     
     
         27 . The method of  claim 26 , further comprising detecting expression levels of genes VGLL3 or c-MAF. 
     
     
         28 . The method of  claim 26 , further comprising detecting expression levels of genes WNT5B CTGF, EZH2, AMACR or MUC1. 
     
     
         29 . The method of  claim 26 , wherein the detection of expression levels of genes F3 and IGFBP3 in the sample is performed by determining the amount of RNA or mRNA. 
     
     
         30 . The method of  claim 29 , wherein the amount of RNA or mRNA is determined by a method selected from the group consisting of microarray technology, Northern blotting and quantitative PCR. 
     
     
         31 . The method of  claim 30 , wherein the amount of RNA or mRNA is determined by quantitative PCR. 
     
     
         32 . The method of  claim 31 , wherein quantitative PCR is conducted by contacting the sample with primer pairs specific for genes F3 and IGFBP3. 
     
     
         33 . The method of  claim 32 , wherein the primer pair specific for gene F3 are primers consisting of the sequences of SEQ ID NOs: 29, 30, or 31. 
     
     
         34 . The method of  claim 32 , wherein the primer pair specific for gene IGFBP3 are primers consisting of the sequences of SEQ ID NOs: 28, 33, 34, 35, 36, or 37. 
     
     
         35 . The method of  claim 26 , wherein the sample is a tumor, blood, plasma, serum, cerebral fluid, urine, semen, exudate or stool sample. 
     
     
         36 . The method of  claim 26 , wherein the sample is a plasma sample. 
     
     
         37 . The method of  claim 26 , wherein the sample is a prostate biopsy tissue sample. 
     
     
         38 . The method of  claim 26 , wherein the gene expression level is determined by quantifying the amount of protein encoded by said genes. 
     
     
         39 . The method of  claim 38 , wherein said amount of protein is determined by use of a method selected from immunohistochemistry, Western blotting, ELISA, RIA and mass spectrometry. 
     
     
         40 . A method diagnosing and treating a low or high risk tumor in a subject with prostate cancer, the method comprising:
 e. obtaining a sample from a subject with prostate cancer:   f. detecting the amount of protein encoded by genes F3 and IGFBP3 in the sample and determining whether the amount of protein encoded by genes F3 and IGFBP3 is higher or lower compared to amount of protein encoded by genes F3 and IGFBP3 from a reference sample;   g. diagnosing the subject with a low risk tumor when the amount of protein encoded by genes F3 and IGFBP3 in the sample is higher compared to amount of protein encoded by genes F3 and IGFBP3 from a reference sample or diagnosing the subject with a high risk tumor when the amount of protein encoded by genes F3 and IGFBP3 in the sample are lower compared to amount of protein encoded by genes F3 and IGFBP3 from a reference sample; and   h. withholding prostatectomy, radiation, chemotherapy, castration, anti-androgen therapy or a combination thereof from the subject with a low risk tumor or administering a lower dose of radiation, chemotherapy anti-androgen therapy or a combination thereof to the subject with a low risk tumor or administering treatment of prostatectomy, radiation, chemotherapy, castration or a combination thereof to the subject with a high risk tumor.   
     
     
         41 . The method of  claim 40 , further comprising the amount of protein encoded by genes VGLL3 or c-MAF. 
     
     
         42 . The method of  claim 40 , further comprising the amount of protein encoded by genes WNT5B CTGF, EZH2, AMACR or MUC1. 
     
     
         43 . The method of  claim 40 , wherein the sample is a tumor, blood, plasma, serum, cerebral fluid, urine, semen, exudate or stool sample. 
     
     
         44 . The method of  claim 43 , wherein the sample is a plasma sample.