Quantitative Urinary Proteomics of UCPPS

Urinary chronic pelvic pain syndrome (UCPPS) is a condition of unknown etiology characterized by pelvic pain, and urinary frequency and/or urgency. As the proximal fluid of this disease, urine is an ideal candidate sample matrix for an unbiased study of UCPPS. In this study, a large, discovery-phase, TMT-based quantitative urinary proteomics analysis of 244 subjects was performed. The subjects included patients with UCPPS (n=82), healthy controls (HC) (n=94) and other chronic pain diseases, termed positive controls (PC) (n=68). Utilizing training and testing cohorts , we identified and validated a small and distinct set of proteins that distinguished UCPPS from HC (n=7) and UCPPS from PC (n=3). Validated UCPPS:HC proteins were predominantly ECM/ECM modifying or immunomodulatory/host defense in nature. Significantly,varying proteins in the UCPPS:HC comparison were overrepresented by members of several dysregulated biological processes including decreased immune cell migration, decreased development of epithelial tissue and increased bleeding. Comparison with the PC cohort enabled evaluation of UCPPS-specific upstream regulators, contrasting UCPPS with other conditions that cause chronic pain. Specific to UCPPS were alterations in the predicted signaling of several upstream regulators, including alpha-catenin, IL6, EGF and TGFB1, among others. These findings advance our knowledge of the etiology of UCPPS and inform potential future clinical translation into a diagnostic panel for UCPPS.