Metabolomic Signatures of Urologic Chronic Pelvic Pain Syndrome

项目总结/摘要 泌尿系统慢性骨盆疼痛综合征（UCPPS）是一种使人衰弱的疾病，困扰着1000万男性， UCPPS包括两种高度流行的慢性泌尿系统疼痛疾病，间质性疼痛， 男性和女性的膀胱炎/膀胱疼痛综合征（IC/BPS）和慢性前列腺炎/慢性盆腔疼痛 综合征（CP/CPPS）。UCPPS主要表现为使人衰弱的症状，其特征为 尿急、尿频和疼痛。不幸的是，导致UCPPS的生物学机制 症状仍不清楚。这延误了诊断并限制了治疗的发展。使用质量 基于光谱的代谢组学方法，我们最近发现， （Etio-S）水平确定了女性UCPPS患者的高症状评分亚组。我们假设 Etio-S升高是相关类固醇更普遍扰动的症状。我们还假设， 这仅仅代表了由生物化学上不同的病因引起的多个UCPPS亚组中的一个。在这 研究中，我们将使用最先进的靶向和非靶向代谢组学方法来辨别UCPPS- 从多学科方法研究人类标本中的相关生化特征 慢性盆腔疼痛（MAPP）研究网络。严格的化学鉴定将这些结果与 特定的生理过程，为新的诊断和治疗方法提供基础。针对性 将使用这些研究中样本的代谢物测定来确定治疗应答亚组， 临床试验，改善UCPPS患者护理。一个经验丰富的跨学科研究团队的医生， 分析化学家和数学数据科学家已经组装，以确保严谨性和临床 这一努力的有效性。

Project Summary/Abstract Urologic Chronic Pelvic Pain Syndrome (UCPPS) is a debilitating condition afflicting 10 million men and women in the U.S. UCPPS encompasses two highly prevalent chronic urologic pain disorders, interstitial cystitis/bladder pain syndrome (IC/BPS) in men and women, and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men. UCPPS prominently manifests as debilitating symptoms characterized by urinary urgency, frequency, and pain. Unfortunately, the biological mechanisms contributing to UCPPS symptoms remain unclear. This delays diagnosis and limits therapeutic development. Using a mass spectrometry-based metabolomics approach, we recently found that elevated urinary etiocholanolone sulfate (Etio-S) levels identify a high symptom score subgroup of female UCPPS patients. We hypothesize that elevated Etio-S is symptomatic of a more general perturbation of related steroids. We also hypothesize that this represents just one of multiple UCPPS subgroups arising from biochemically distinctive etiologies. In this study, we will use state-of-the-art targeted and untargeted metabolomics approaches to discern UCPPS- associated biochemical signatures in human specimens from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network. Rigorous chemical identification will connect these results to specific physiological processes, providing the basis for new diagnostic and therapeutic approaches. Targeted metabolite assays of samples from these studies will be used to identify treatment-responsive subgroups in clinical trials, improving UCPPS patient care. An experienced interdisciplinary research team of physicians, analytical chemists, and mathematical data scientists has been assembled to ensure the rigor and clinical validity of this effort.