This proposal is a renewal of our EDRN Biomarker Reference Laboratory (BRL) which is located within the Clinical Chemistry Division (CCD) of the Johns Hopkins Medical Laboratories (JHML) at the Johns Hopkins Hospital. The BRL will continue to serve as a network resource for clinical and laboratory validation of biomarkers, which includes technological development and assay refinement. The JHML are certified by the College of American Pathologist (CAP) and regulated by CLIA (Clinical Laboratory Improvement Amendments of 1988). As such, the JHML follow stringent, good laboratory practice (GLP) guidelines for quality control and quality assurance. The proposed product development will be conducted at the Center for Biomarker Discovery and Translation (CBDT) at The Johns Hopkins University. The project goal is to validate serum proteomic biomarkers, including two biomarkers discovered in our current EDRN BRL developmental study, for the prediction of aggressive prostate cancer in men prior to prostate biopsy. The product AGPC is an in vitro diagnostic multivariate index assay (IVDMIA) that combines a panel of biomarkers into a single-valued numerical index score. We have assembled a strong team of research and clinical scientists with many years of experience with cancer biomarkers and in technology development, study design, bioinformatics, validation, and translation. Dr. Chan, the PI, is the Director of both CCD and CBDT. He has over 30 years of experience in clinical chemistry and has conducted many (> 75) research studies funded by industry on cancer diagnostics leading to the approval by the FDA. Since the inception of the EDRN in 2000, five EDRN developed assays have been approved by the FDA for clinical use. Of these five, our BRL led the development of serum OVA1 for ovarian cancer, serum proPSA (phi) for prostate cancer, and served as the reference lab for the urine PCA3 study for prostate cancer. In fact, OVA1 which is based on our original multiplex proteomic study published in Cancer Research, was the first proteomic IVDMIA ever cleared by the FDA for clinical use. In addition, three leading diagnostics/biotechnology companies have agreed to collaborate with us in our product development proposal. In this renewal, we plan to continue our strong commitment to the EDRN mission through network collaborations, and provide leadership in biomarker validation, technology/assay improvement, and product development. With this multi-disciplinary team of scientists, the BRL at Johns Hopkins offers the best opportunity for the success of cancer biomarker validation and translation into the clinic for the early detection of cancer.