A tumor is an unwanted organ, progressively formed through stepwise accumulation of a number of events, genetic and epigenetic, arising in a single cell over a long time interval (1). An urgent yet challenging priority in cancer biology is to detect or identify these sequential events early enough through characterizing cancer-associated genes and their protein products. At a specific stage, biomarkers reflect the physiologic state of a cell and might be vital for the identification of early cancer and subjects at risk of developing cancer. Molecular profiling of cancer cell gene expression could prove to be instrumental in identifying the sensitivity of cancer cells to specific therapeutic interventions and, hence, serves as an efficient tool in discovering more molecular biomarkers for cancer control and prevention.

Prostate cancer (CaP) is responsible for 3% of all deaths in the Western world in men over 55 yr of age. Biomarkers have become an important diagnostic tool in prostate cancer. The discovery of the serum marker prostate-specific antigen (PSA) and its test have revolutionized the early detection of CaP (2). Although PSA is effective in identifying men who may have CaP, it is often elevated in men with benign prostatic hyperplasia, prostatitis, and other nonmalignant disorders (2). The prognostic value of the Gleason score is limited by the fact that the vast majority of prostate cancer patients presented with moderately differentiated tumors (e.g., Gleason score of 6) in the PSA era, limiting the prognostic utility of morphologic features for this subgroup of patients. Given these drawbacks, identification of additional CaP-specific molecular markers is thus needed to refine the diagnosis as well as prognosis for CaP. CaP-associated molecular genetic alterations are being uncovered through (1) analyses of genes commonly involved in human cancer, (2) positional cloning of putative genes on frequently affected chromosome loci in CaP, and (3) gene expression profiling of normal and tumor specimens of patients with CaP (3).

With the advent and recent successes in functional genomics and proteomics, we are experiencing growing interest in discovering more molecular-based prognostic factors that could be utilized to assay the original needle biopsy specimen to tailor the primary treatment for individual prostate cancer patients (4-7). As targeted therapy in oncology becomes increasingly powerful, there is a significant interest in finding prognostic markers in prostate cancer that could be used as targets for novel biotherapies. Many molecular- and genetic-based biomarkers have been discovered over the last two decades and are summarized in Table 1 and in ref. 8. This chapter discusses a series of existing and emerging molecular-based prognostic markers generated from the ongoing research in genomic, genetic, and proteomic approaches that identify molecular signatures such as gene expression profiles.

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