Multiplexed biomarker panels for early detection of prostate cancer

DESCRIPTION (provided by applicant): The goal of the proposed work is development of sensitive diagnostic serological assay panels for detection of early stage prostate cancer. Currently, the only biomarker used in prostate cancer diagnosis is the measurem ent of prostate specific antigen (PSA) in patient serum. PSA levels can be elevated by various conditions, and are often not at the diagnostically critical levels when cancer develops. There is a need for alternative biomarkers to more efficiently diagnose prostate cancer, particularly for early detection when aggressive treatments would be most effective. Approaches that detect autoimmune responses to cancer-related antigens are being developed as an effective means of early cancer detection, detectible be fore measurable amount of the antigens they react with accumulate for direct antigen detection. Prostate cancer- specific immune responses are being identified by Chinnaiyan et al. using several approaches, including screening with prostate cancer-specific cDNA expression systems as well as known prostate cancer related proteins. Great value is seen in the ability of these antigens to specifically and sensitively detect cancer when used in combination, superior to PSA-based determinations. This proposal sug gests combining MSD's sensitive Multi-Array(r) technology with the extensive prostate cancer biomarker expertise and resources of Dr. Arul Chinnaiyan and colleagues (University of Michigan), to develop highly specific and sensitive multiplex serological sc reening panels for early detection of prostate cancer. Multiple distinct antigens of interest (antigen-expressing phage particles, or purified peptides) will be immobilized in MSD Multi-Array(r) panels, which can accommodate 1-25 assays/well of a 96-well p late. These panels will be optimized for ability to detect specific humoral responses in prostate cancer patient samples, allowing multiple simultaneous determinations per well. MSD multiplex panels for serum-based measurements have shown sensitivities as low as 0.1 pg/mL, 3-5 orders of magnitude dynamic range, rapid throughput, and minimal sample usage ( 25 microliters/well), factors which would be critical in developing successful serological screening panels for the proposed study. The proposed academic/ industry collaboration addresses NCI goals of translational medicine, by advancing potential biomarkers from discovery towards clinical applications using a versatile and robust assay platform, and the IMAT goal of evaluating technologies that are ready fo r initial clinical or laboratory application in cancer research.