Despite the success of using PSA as a prostate cancer biomarker for more than 25 years, it is clear that weneed a marker that is both specific for the disease and that can differentiate the disease with the potential tokill from that which will not result in clinical significance. Utilizing proteomics focused on the nuclear matrix,we have identified alterations associated with prostate cancer. One such change, EPCA-2 is the focus ofthis application. The assay which detects serum levels of EPCA-2 has been shown to be specific for thedisease and is able to discriminate between disease inside the prostate at the time of surgery and diseasewhich has spread outside of the gland. The hypothesis being evaluated in this project is that EPCA-2 canserve as a prostate cancer biomarker that can differentiate between aggressive and non-aggressiveprostate cancer. The goal of this project is translation of prostate cancer biomarkers (e.g. EPCA-2) intopatient care for prostate cancer within a multi-institutional SPORE platform. The following specific aims areproposed to address this hypothesis: 1) to determine the ability of EPCA-2 to differentiate betweenpopulations of Gleason score 6, 7 and 8-10 in a population of Johns Hopkins Hospital patients as well as inan inter-SPORE study; 2) to analyze if serum EPCA-2 levels can identify which men, who at the time ofsurgery have Gleason 7 prostate cancer and a minimum of 10 year follow-up, have biochemical recurrence(PSA) from those with non-recurrent disease. These studies will consist of sample sets both from JohnsHopkins as well as other available SPORE sample sets; and 3) to begin to determine the functional role ofthe EPCA-2 protein in the disease process as well as the mechanism by which it is released into the serum.
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