Benign Prostatic Hyperplasia (BPH) is a disease of unknown etiology that significantly affects the quality of life in aging men. Histologic BPH may present itself either as symptomatic or asymptomatic in nature. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone tissue have been analyzed using microarrays. A set of 511 differentially expressed genes distinguished symptomatic and asymptomatic BPH. This genetic signature separates BPH from normal tissue but does not appear to change with age. This analysis resulted in the identification of several targets, which appear to differentiate BPH from individuals with symptoms from those with histologic BPH. As a Biomarker Unit of the MTOPS Prostate Sample Analysis Consortium we propose to both utilize these markers in a cooperative nature to analyze the tissue and serum samples collected as part of the Medical Therapy of Prostatic Symptoms clinical trial. Our Biomarker Unit will work closely together with the existing MTOPS Data Coordinating Center, the Pathology Coordinating Center as well as the other awarded Biomarker Units. We hypothesize that the genetic markers that we have identified may correlate with the occurrence of BPH as well as the severity of the BPH, responses to pharmacological agents as well as with clinical parameters obtained as part of the study. This hypothesis will be addressed by conducting the following specific aims: 1) to analyze the expression of JM-27, BMP-5 (list other markers) as well as other markers in biopsy samples obtained from the MTOPS trial as well as normal and BPH (symptomatic and asymptomatic) tissues in our bank and to correlate the above-described markers with both response to therapy and symptom progression ; 2) to develop serum-based methodologies for testing the expression of the above-described markers in patient samples obtained from the MTOPS trial as well as from normal and BPH (symptomatic and asymptomatic) individuals from our Institution; and 3) to further develop a system by which other markers developed and prioritized by the MTOPS Consortium can be analyzed. As a component of the MTOPS Consortium, these studies should provide the development of novel biomarkers with utility in diagnosing and characterizing BPH.
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