Urinary Metabolites in IC PBS Diagnosis

描述（由申请人提供）：本项目的目标是识别和验证间质性膀胱炎/膀胱疼痛综合征（IC/PBS）相关的尿液代谢物。IC/PBS是一种衰弱性疾病，在没有其他可识别病因的情况下，表现为一系列症状，包括膀胱疼痛、尿急、尿频、夜尿和小排尿量。IC/PBS的诊断仍然依赖于主观参数，导致准确分型患者极其困难。我们的中心假设是IC/PBS患者尿液中的IC/PBS相关代谢物可以将患者与对照组区分开来，并且其水平与临床症状相关。这一假设是基于我们的质子核磁共振（NMR）光谱研究结果，发现尿液代谢物似乎可以将IC/PBS患者与健康对照组区分开来。我们建议以这些结果为基础，确定候选尿液代谢物是否可以作为IC/PBS的诊断指标。为了验证这一假设，我们将（目标1）使用两个独立的平台，质子核磁共振波谱和四极杆飞行时间（Q-TOF）质谱鉴定尿液中IC/ pbs相关代谢物。我们将确定候选代谢物是否能将IC/PBS患者与对照组区分开来，并与临床严重程度（包括慢性膀胱疼痛）相关。为了更深入地了解这种情况的潜在生物学性质，我们将使用综合生物信息学识别与IC/PBS相关的病理网络。我们还将（目标2）创建雪松-西奈医学中心IC/PBS尿液生物库，并将对IC/PBS代谢物进行初步验证研究。我们的长期目标包括确定诊断性尿液生物标志物，这些生物标志物可以作为诊断IC/PBS的非侵入性和准确的手段，并将这些患者与其他膀胱或盆底疾病患者进行分层。我们也寻求长期发展

DESCRIPTION (provided by applicant): The goal of this project is to identify and validate interstitial cystitis/painful bladder syndrome (IC/PBS)- associated urinary metabolites. IC/PBS is a debilitating condition that presents with a constellation of symptoms including bladder pain, urinary urgency, frequency, nocturia, and small voided volumes in the absence of other identifiable etiologies. The diagnosis of IC/PBS remains dependent on subjective parameters, leading to extreme difficulties in accurately phenotyping patients. Our central hypothesis is that IC/PBS- associated metabolites in the urine of IC/PBS patients can segregate patients from control subjects, and that their levels are correlated with clinical symptoms. This hypothesis is based on our proton nuclear magnetic resonance (NMR) spectroscopy findings identifying urine metabolites that appear to stratify IC/PBS patients from healthy controls. We propose to substantially build on these results and determine whether candidate urine metabolites are diagnostic indicators of IC/PBS. To test this hypothesis we will (Aim 1) Identify IC/PBS-associated metabolites in urine using two independent platforms, proton NMR spectroscopy and quadrupole time-of-flight (Q-TOF) mass spectrometry. We will determine whether candidate metabolites segregate IC/PBS patients from control subjects, and are associated with clinical severity, including chronic bladder pain. In order to achieve a deeper understanding of the underlying biological nature of this condition, we will identify pathologic networks associated with IC/PBS using integrative bioinformatics. We will also (Aim 2) create a Cedars-Sinai Medical Center IC/PBS urine biorepository and will conduct preliminary validation studies of IC/PBS metabolites. Our long-term goals include the identification of diagnostic urinary biomarkers that can serve as non-invasive and accurate means of diagnosing IC/PBS and stratifying these patients from patients with other bladder or pelvic floor conditions. We also seek in the long term to validate molecular targets for therapeutic strategies. This study has a significant potential clinical impact because results may lead to clinical methods to increase diagnostic accuracy and an improved understanding of the molecular basis of IC/PBS and its relationship to urologic conditions with overlapping symptoms.