Biomarkers for prostate cancer and methods using the same

Abstract

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

What is claimed is: 
     
         1 . A method of distinguishing low grade prostate cancer from high grade prostate cancer in a subject having prostate cancer, comprising: analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for low grade prostate cancer and/or high grade prostate cancer in the sample, wherein the one or more biomarkers are selected from Tables 3, 8, 11, 20, and/or 26 and comparing the level(s) of the one or more biomarkers in the sample to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or to high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer in order to determine whether the subject has low grade or high grade prostate cancer. 
     
     
         2 . The method of  claim 1 , wherein the biological sample is prostate tissue and the one or more biomarkers are selected from Table 3. 
     
     
         3 . The method of  claim 1 , wherein the biological sample is blood plasma and the one or more biomarkers are selected from Table 8 and/or 26. 
     
     
         4 . The method of  claim 1 , wherein the biological sample is urine and the one or more biomarkers are selected from Table 11 and/or 20. 
     
     
         5 . The method of  claim 1 , wherein the one or more biomarkers are selected from those biomarkers in Tables 3, 8, 11, 20, and/or 26 having p values of less than 0.05 and/or those biomarkers in Tables 3, 8, 11, 20, and/or 26 having q values of less than 0.10. 
     
     
         6 . The method of  claim 1 , wherein the one or more biomarkers comprise one or more biomarkers selected from the group consisting of sarcosine, citric acid, spermine, and malic acid. 
     
     
         7 . The method of  claim 1 , wherein the comparing step comprises comparing a ratio of the levels of one or more biomarkers in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 having p values of less than 0.05 and/or those biomarkers in Tables 1, 2, 4, 5, 6, 7, 9, 10, 13, 15, 18, 22, and/or 24 having q values of less than 0.10 to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer in order to determine whether the subject has low grade or high grade prostate cancer. 
     
     
         8 . The method of  claim 7 , wherein the ratio of the levels of one or more biomarkers comprises the level of a biomarker selected from the group consisting of sarcosine, spermine, and malic acid. 
     
     
         9 . The method of  claim 1 , wherein the comparing step comprises comparing a ratio of the levels of one or more biomarkers to low grade prostate cancer-positive reference levels that distinguish over high grade prostate cancer and/or high grade prostate cancer-positive reference levels that distinguish over low grade prostate cancer in order to determine whether the subject has low grade or high grade prostate cancer, wherein the ratio is selected from the group consisting of the ratio of levels of sarcosine and citric acid, sarcosine and spermine, and citric acid and malic acid. 
     
     
         10 . The method of  claim 1 , wherein the sample is analyzed using one or more techniques selected from the group consisting of gas chromatography, liquid chromatography, mass spectrometry, ELISA, and antibody linkage. 
     
     
         11 . A method of monitoring progression/regression of prostate cancer in a subject comprising: analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer in the sample, wherein the one or more biomarkers are selected from Tables 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26 and the first sample is obtained from the subject at a first time point; analyzing a second biological sample from a subject to determine the level(s) of the one or more biomarkers, wherein the second sample is obtained from the subject at a second time point; and comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to monitor the progression/regression of prostate cancer in the subject. 
     
     
         12 . The method of  claim 11 , wherein the method further comprises comparing the level(s) of one or more biomarkers in the first sample, the level(s) of one or more biomarkers in the second sample, and/or the results of the comparison of the level(s) of the one or more biomarkers in the first and second samples to prostate cancer-positive and/or prostate cancer-negative reference levels of the one or more biomarkers. 
     
     
         13 . The method of  claim 11 , wherein the sample is analyzed using one or more techniques selected from the group consisting of gas chromatography, liquid chromatography, mass spectrometry, ELISA, and antibody linkage. 
     
     
         14 . A method of assessing the efficacy of a composition for treating prostate cancer comprising: analyzing, from a subject having prostate cancer and currently or previously being treated with a composition, a biological sample to determine the level(s) of one or more biomarkers for prostate cancer selected from Tables 1, 2, 4, 5, 6, 7, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; and comparing the level(s) of the one or more biomarkers in the sample to (a) levels of the one or more biomarkers in a previously-taken biological sample from the subject, wherein the previously-taken biological sample was obtained from the subject before being treated with the composition, (b) prostate cancer-positive reference levels of the one or more biomarkers, and/or (c) prostate cancer-negative reference levels of the one or more biomarkers. 
     
     
         15 . The method of  claim 14 , wherein the sample is analyzed using one or more techniques selected from the group consisting of gas chromatography, liquid chromatography, mass spectrometry, ELISA, and antibody linkage. 
     
     
         16 . A method for assessing the efficacy of a composition in treating prostate cancer, comprising: analyzing a first biological sample from a subject to determine the level(s) of one or more biomarkers for prostate cancer selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26, the first sample obtained from the subject at a first time point; administering the composition to the subject; analyzing a second biological sample from the subject to determine the level(s) of the one or more biomarkers, the second sample obtained from the subject at a second time point after administration of the composition; comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the efficacy of the composition for treating prostate cancer. 
     
     
         17 . The method of  claim 16 , wherein the sample is analyzed using one or more techniques selected from the group consisting of gas chromatography, liquid chromatography, mass spectrometry, ELISA, and antibody linkage. 
     
     
         18 . A method of assessing the relative efficacy of two or more compositions for treating prostate cancer comprising: analyzing, from a first subject having prostate cancer and currently or previously being treated with a first composition, a first biological sample to determine the level(s) of one or more biomarkers selected from Tables 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 15, 18, 20, 22, 24, and/or 26; analyzing, from a second subject having prostate cancer and currently or previously being treated with a second composition, a second biological sample to determine the level(s) of the one or more biomarkers; and comparing the level(s) of one or more biomarkers in the first sample to the level(s) of the one or more biomarkers in the second sample in order to assess the relative efficacy of the first and second compositions for treating prostate cancer. 
     
     
         19 . The method of  claim 18 , wherein the sample is analyzed using one or more techniques selected from the group consisting of gas chromatography, liquid chromatography, mass spectrometry, ELISA, and antibody linkage.