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      Delineation of prognostic biomarkers in prostate cancer.

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          Abstract

          Prostate cancer is the most frequently diagnosed cancer in American men. Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer, but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and lead to an improved classification of prostate cancer. Using microarrays of complementary DNA, we examined gene-expression profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of normal adjacent prostate (NAP), BPH, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Here we establish many associations between genes and prostate cancer. We assessed two of these genes-hepsin, a transmembrane serine protease, and pim-1, a serine/threonine 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 outcome. Thus, the integration of cDNA microarray, high-density tissue microarray, and linked clinical and pathology data is a powerful approach to molecular profiling of human cancer.

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          Author and article information

          Journal
          Nature
          Nature
          Springer Science and Business Media LLC
          0028-0836
          0028-0836
          Aug 23 2001
          : 412
          : 6849
          Affiliations
          [1 ] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
          Article
          35090585
          10.1038/35090585
          11518967
          52777183-4f9c-4fbf-bcca-2443d0608e86
          History

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