Genetic signatures to predict prostate cancer metastasis and identify tumor aggressiveness

Abstract

The present invention relates to methods, systems and kits for the diagnosis, prognosis and the determination of cancer progression of prostate cancer in a subject. The invention also provides clinically useful genomic classifiers for predicting prostate cancer metastasis and identifying tumor aggressiveness. The methods, systems and kits can provide expression-based analysis of biomarkers for purposes of predicting metastatic disease and lethal prostate cancer in a subject. Further disclosed herein, in certain instances, are probe sets for use in predicting prostate cancer metastasis in a subject. Classifiers for predicting prostate cancer metastasis are provided. Methods of treating cancer based on tumor aggressiveness are also provided. The methods and classifiers of the present invention are also useful for predicting early prostate cancer metastasis.

1 . A method comprising:
 a) obtaining a biological sample from a subject; and   b) detecting the presence or assaying an expression level in the sample from the subject for a plurality of target sequences, wherein the plurality of target sequences is selected from Table 1 or SEQ ID NOs: 1-1815.   
     
     
         2 . The method of  claim 1 , wherein the plurality of target sequences comprises a coding and/or non-coding target. 
     
     
         3 . The method of  claim 1 , wherein the plurality of target sequences comprises a nucleic acid sequence. 
     
     
         4 . The method of  claim 3 , wherein the nucleic acid sequence is a DNA sequence or an RNA sequence. 
     
     
         5 . The method of  claim 1 , wherein the plurality of target sequences comprises at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 or 60 target sequences selected from Table 1 or SEQ ID NOs: 1-1815. 
     
     
         6 . The method of  claim 1 , wherein the subject has cancer. 
     
     
         7 . The method of  claim 6 , wherein the cancer is selected from the group consisting of skin cancer, lung cancer, colon cancer, pancreatic cancer, prostate cancer, liver cancer, thyroid cancer, ovarian cancer, uterine cancer, breast cancer, cervical cancer, kidney cancer, epithelial carcinoma, squamous carcinoma, basal cell carcinoma, melanoma, papilloma, and adenomas. 
     
     
         8 . The method of  claim 1 , further comprising administering a treatment to the subject. 
     
     
         9 . The method of  claim 8 , wherein the treatment is selected from the group consisting of surgery, chemotherapy, radiation therapy, immunotherapy/biological therapy, and photodynamic therapy. 
     
     
         10 . The method of  claim 1 , wherein the biological sample is a urine sample, a blood sample or a prostate tumor sample. 
     
     
         11 - 19 . (canceled) 
     
     
         20 . A kit for predicting cancer aggressiveness or risk of metastasis, the kit comprising agents for assaying an expression level of a plurality of genes, wherein said plurality of genes comprises one or more genes selected from Table 1 or SEQ ID NOs: 1-1815. 
     
     
         21 . A system for analyzing a cancer, comprising:
 a probe set comprising a plurality of target sequences, wherein the plurality of target sequences hybridizes to one or more targets selected from Table 1 or SEQ ID NOs: 1-1815; or the plurality of target sequences comprises one or more targets selected from Table 1 or SEQ ID NOs: 1-1815; and   a computer model or algorithm for analyzing an expression level and/or expression profile of the target hybridized to the probe in a sample from a subject suffering from prostate cancer.   
     
     
         22 . A probe set for prognosing or diagnosing cancer in a subject, the probe set comprising a plurality of probes for detecting a plurality of target nucleic acids, wherein the plurality of target nucleic acids comprises one or more gene sequences, or complements thereof, of genes selected from Table 1.