Biomarkers for Molecular-Based Decision-Making in Diagnosis and Treatment of Inte

 描述（申请人提供）：间质性膀胱炎/膀胱疼痛综合征/膀胱疼痛综合征（IC/PBS/BPS;以下简称IC）是一种令人烦恼的异质性下尿路疾病，目前由国际尿失禁协会定义为：“一种不愉快的感觉（疼痛、压力、不适）感觉与膀胱相关，与持续时间超过6周的下尿路症状相关，在没有感染或其他可识别原因的情况下”。国家糖尿病、消化和肾脏疾病研究所（NIDDK）和欧洲间质性膀胱炎研究学会（ESSIC）也提出了诊断标准。这些组织的标准略有不同，这使得IC的预测发病率和患病率可变。这种诊断的不确定性进一步被IC与其他功能性疼痛综合征的重叠所混淆，包括纤维肌痛、肠易激综合征、慢性前列腺炎/慢性骨盆疼痛和vuvlodynia（有时与膀胱病因疼痛混淆），这些症状被认为具有相似的病理生理学。一种以临床相关的方式快速分类/诊断IC患者的方法，其还预测对治疗的反应，这将是真实的临床资产，因为最合适的、患者特异性的治疗可以在过程的早期开始。具有定义特定IC亚型的生物标志物可以极大地促进诊断和治疗。使用分子工具，如相关组织中的基因表达谱，提供了一种可行的方法。 和有效的方法来鉴定这些生物标志物。我们假设IC患者可以根据症状和/或临床结果与患者膀胱活检组织基因表达谱的相关性分为临床相关组。我们进一步 假设这些生物标志物可以是预测性、预后性和/或诊断性的。我们将通过将最初基于膀胱容量指定的IC患者亚组与这些亚组的基因表达谱相关联来检验这些假设（具体目标1）。我们还将膀胱组织基因表达谱与同一IC患者的外周血基因表达相关联，以确定外周血是否含有IC亚组的临床有用生物标志物（具体目标2）。

 DESCRIPTION (provided by applicant): Interstitial cystitis/painful bladder syndrome/bladder pain syndrome (IC/PBS/BPS; hereafter IC) is a vexing and heterogeneous lower urinary tract disorder, currently defined by the International Continence Society as: "an unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six weeks duration, in the absence of infection or other identifiable causes". Diagnostic criteria have also been set forth by the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) and the European Society for Study of Interstitial Cystitis (ESSIC). Criteria from each of these organizations differ slightly, which renders the projected incidence and prevalence numbers of IC variable. This diagnostic uncertainty is further confounded by the overlap of IC with other functional pain syndromes including fibromyalgia, irritable bowel syndrome, chronic prostatitis/chronic pelvic pain, and vuvlodynia (sometimes confused with pain of bladder etiology), which have been posited to have similar pathophysiology. A method to quickly categorize/diagnose IC patients in a clinically relevant way that also predicts response to treatment would be a real clinical asset in that the most appropriate, patient-specific, therapy could be initiated early on in the process. Having biomarkers that define a specific IC subtype(s) could greatly facilitate diagnosis and treatment. The use of molecular tools, like gene expression profiling in relevant tissues, provides a feasible and effective approach for the identification of these biomarkers. We hypothesize that patients with IC can be categorized into clinically relevant groups based on the correlation of symptoms and/or clinical findings to gene expression profiles from patient bladder biopsy tissue. We further hypothesize that these biomarkers may be predictive, prognostic, and/or diagnostic. We will test these hypotheses by correlating subgroups of IC patients, designated based initially on bladder capacity, with gene expression profiles of those subgroups (Specific Aim 1). We will also correlate bladder tissue gene expression profiles with peripheral blood gene expression within the same IC patients to determine whether the peripheral blood harbors a clinically useful biomarker for IC sub-grouping (Specific Aim 2).