Delineation of prognostic biomarkers in prostate cancer

Prostate cancer is the most frequently diagnosed cancer in American men(1,2 ). Screening for prostate-specific antigen (PSA) has led to earlier detecti on of prostate cancer(3), but elevated serum PSA levels may be present in n on-malignant conditions such as benign prostatic hyperlasia (BPH). Characte rization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidat e clinical biomarkers, and lead to an improved classification of prostate c ancer(4-6). Using microarrays of complementary DNA, we examined gene-expres sion profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of n ormal adjacent prostate (NAP), BPH, localized prostate cancer, and metastat ic, hormone-refractory prostate cancer were determined. Here we establish m any associations between genes and prostate cancer. We assessed two of thes e genes-hepsin, a transmembrane serine protease, and pim-1, a serine/threon ine kinase-at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate-cancer specimens. Expression of hepsin and pim-1 proteins was significantly correlated with measures of clinical o utcome. Thus, the integration of cDNA microarray, high-density tissue micro array, and linked clinical and pathology data is a powerful approach to mol ecular profiling of human cancer.