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

用于诊断和治疗肠道疾病的基于分子的决策的生物标志物

• 批准号: 8953797
• 负责人: STEPHEN WALKER
• 金额: $ 23.25万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8953797
• 关键词: Biological; Biological Markers; Biopsy; Bladder; Bladder Tissue; Blood; Chronic Prostatitis; Clinic; Clinical; Cystectomy; Data; Decision Making; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Esthesia; Etiology; European; Evidence based treatment; Exhibits; Fibromyalgia; Functional disorder; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Goals; Grouping; Incidence; Infection; International; Interstitial Cystitis; Irritable Bowel Syndrome; Lower urinary tract; Methods; Molecular; Molecular Profiling; National Institute of Diabetes and Digestive and Kidney Diseases; Outcome; Pain; Pathologic Processes; Patients; Pattern; Pelvic Pain; Pelvic floor dysfunction; Phenotype; Pilot Projects; Prevalence; Process; Societies; Subgroup; Symptoms; Syndrome; Testing; Time; Tissue-Specific Gene Expression; Tissues; Treatment Efficacy; Uncertainty; Urologic Diseases; Urology; base; bladder pain; chronic pelvic pain; clinically relevant; cohort; design; disorder subtype; evidence base; lower urinary tract symptoms; peripheral blood; pressure; prognostic; public health relevance; research study; response; tool

 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).

 描述（由申请人提供）：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）是一种令人烦恼且异质的下尿路疾病，目前国际尿控协会将其定义为：“一种不愉快的感觉” （疼痛、压力、不适）被认为与膀胱有关，与持续时间超过六周的下尿路症状相关，在没有感染或其他可识别的原因”。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) 也制定了诊断标准。这些组织的标准略有不同，使得 IC 变量的预计发病率和患病率数字因 IC 与其他功能性疼痛综合征（包括纤维肌痛、肠易激综合征、慢性疼痛）的重叠而进一步混淆。前列腺炎/慢性盆腔疼痛和阴道痛（有时与膀胱疼痛病因混淆），被认为具有相似的病理生理学，一种以临床相关方式快速分类/诊断 IC 患者的方法，同时也可以预测对治疗的反应。真正的临床资产是，可以在该过程的早期开始最合适的、针对患者的治疗，具有定义特定 IC 亚型的生物标志物可以极大地促进分子诊断和治疗。相关组织中的基因表达谱等工具提供了可行的方法 我们进一步寻求根据症状和/或临床发现与患者膀胱活检组织基因表达谱的相关性将 IC 患者分为临床相关组。 坚持认为这些生物标志物可能具有预测性、预后性和/或诊断性，我们将通过将最初根据膀胱容量指定的 IC 患者亚组与这些亚组的基因表达谱相关联来测试这些假设（具体目标 1）。将同一 IC 患者的膀胱组织基因表达谱与外周血基因表达相关联，以确定外周血是否含有临床上有用的 IC 亚组生物标志物（具体目标 2）。