Proteomics Approaches to Benign Prostatic Hyperplasia.

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DESCRIPTION (provided by applicant): This application is in response to RFA-DK-02-017: MPSA Consortium. The major goal of this application is to assemble a cross-disciplinary group of investigators to identify potential biomarkers that can distinguish benign prostatic hyperplasia (BPH) from prostate cancer and normal prostate. The second goal of this application is to validate these potential biomarkers in a larger context, including the use of well-characterized samples from the Medical Therapy of Prostatic Symptoms (MTOPS) clinical trial. Specifically, we will: 1. Identify disease specific biomarkers in microdissected prostate tissues by surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry; 2. Identify and characterize isoforms of prostate specific antigen (PSA) and the various members of the human kallikrein family by immunosorption and tandem mass spectrometry (ms/ms)-based sequence identification; 3. Identify secreted proteins in serum of patients with benign prostatic hyperplasia and prostate cancer by SELDI-TOF approaches, and to mine these proteomics data to create predictive models that can stratify samples according to clinical information by using a biomarker patterns recognition software and longitudinal screening algorithms; 4. Identify potential chromosomal locations of under- and over-expressed genes between BPH, prostate cancer, and normal prostate by using a simple rapid overview of expression patterns on metaphase chromosomes; and 5. Collaborate with other investigators in the MPSA Consortium by developing a BWH Prostate Bio-Specimen and Informatics Repository consisting of: 1) the acquisition and maintenance of BWH specimens, both serum and limited tissues; 2) the maintenance and update of a virtual clinical information and outcome database; and 3) the storage of remaining RNA, cDNA, and/or protein extracts from dissected specimens.