Circulating microRNA as a novel biomarker for inflammatory bowel disease

循环 microRNA 作为炎症性肠病的新型生物标志物

• 批准号: 8370324
• 负责人: Adam Matthew Zahm
• 金额: $ 5.43万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2014-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8370324
• 关键词: Abdominal Pain; Abscess; Affect; Age; Biological Markers; Biopsy; Biopsy Specimen; Blood Tests; Body Weight decreased; Celiac Disease; Cells; Child; Child health care; Childhood; Chronic; Clinical; Clinical Management; Clinical Research; Colonoscopy; Crohn' s disease; Cross-Sectional Studies; Data; Development; Diagnosis; Diagnostic; Diarrhea; Disease; Endoscopy; Equilibrium; Failure; Feces; Fistula; Freezing; Gender; Goals; Gold; Growth; Healed; Hemorrhage; Hospitalization; Inflammation; Inflammatory Bowel Diseases; Intestinal Diseases; Knowledge; Laboratories; Lead; Location; Longitudinal Studies; Malignant Neoplasms; Measurement; Measures; Medical Research; MicroRNAs; Microarray Analysis; Operative Surgical Procedures; Outcome; Participant; Patients; Pediatric Hospitals; Philadelphia; Physicians; Pilot Projects; Plasma; Population Control; Preparation; Procedures; Property; RNA; Receiver Operating Characteristics; Regimen; Research; Research Personnel; Research Training; Reverse Transcription; Ribonucleases; Risk; Sampling; Serum; Severity of illness; Surrogate Markers; Surveys; Symptoms; System; Testing; Time; Tissues; Training; Training Activity; Training Programs; Ulcerative Colitis; base; diagnosis evaluation; disease phenotype; disorder subtype; experience; healing; improved; indexing; novel; novel diagnostics; predictive modeling; rectal; response; skills; symposium; therapy development

DESCRIPTION (provided by applicant): The objective of this proposal is to provide the applicant with exemplary translational medical research training in the development of diagnostic biomarkers of pediatric disease. To achieve this objective, a training regimen within the scope of inflammatory bowel disease (IBD) had been developed, consisting of research aims and substantial training activities. IBD is an intestinal disorder characterized by chronic inflammation, resulting in a variety of uncomfortable and even dangerous symptoms including diarrhea, weight loss, growth failure, rectal bleeding, abscesses, strictures, or fistulas. IBD comprises two disease types, Crohn's disease (CD) and ulcerative colitis (UC), and is one of the most serious diseases affecting the health of children; the peak diagnosis period for both CD and UC occurs during childhood (1, 2). Due to a lack of conclusive biomarkers, the gold standard for diagnosis and evaluation of IBD is endoscopy/colonoscopy, although this invasive and costly procedure is associated with risks to the patient. Recently, circulating microRNA (miRNA) profiles with diagnostic potential have been described for several conditions, including cancer (3-8). As described in the Preliminary Studies, we have identified a set of circulating miRNAs that are significantly altered in CD. The specific research aims of the proposal are: 1) to identify CD- and UC-specific circulating miRNA profiles for use as diagnostic biomarkers of pediatric IBD and 2) to assess the utility of circulating miRNAs as predictors of outcome and surrogate markers of pediatric IBD. Sera will be obtained from patients presenting for endoscopy/colonoscopy for suspected IBD at the Pediatric IBD Center at the Children's Hospital of Philadelphia. IBD-specific miRNAs will be identified by microarray and confirmed in large, independent sample sets. The diagnostic potential of circulating miRNAs will be compared to current IBD biomarkers using receiver operating characteristic analysis. Longitudinal studies will be performed to determine the utility of circulating miRNAs as surrogate markers and predictors of outcome. In addition to the research aims, a comprehensive training program has been developed; this plan includes coursework in clinical research and seminars and conferences on topics including biomarker discovery, microarray analysis, and professional development. Overall, the proposed training regimen constitutes a balanced introduction to the skills and experience necessary to become a successful independent research investigator and may lead to a dramatic reduction in the need for invasive testing in the diagnosis and clinical management of IBD in children.

描述（由申请人提供）：本提案的目的是为申请人提供儿科疾病诊断生物标志物开发方面的示范性转化医学研究培训。为了实现这一目标，制定了炎症性肠病（IBD）范围内的培训方案，包括研究目标和实质性培训活动。 IBD 是一种以慢性炎症为特征的肠道疾病，导致各种不舒服甚至危险的症状，包括腹泻、体重减轻、生长障碍、直肠出血、脓肿、狭窄或瘘管。 IBD包括克罗恩病（CD）和溃疡性结肠炎（UC）两种疾病类型，是影响儿童健康最严重的疾病之一； CD 和 UC 的诊断高峰期都发生在儿童时期 (1, 2)。由于缺乏确凿的生物标志物，诊断和评估 IBD 的金标准是内窥镜检查/结肠镜检查，尽管这种侵入性且昂贵的手术会给患者带来风险。最近，具有诊断潜力的循环 microRNA (miRNA) 谱已被描述用于多种疾病，包括癌症 (3-8)。正如初步研究中所述，我们已经鉴定出一组在 CD 中发生显着改变的循环 miRNA。该提案的具体研究目标是：1) 确定 CD 和 UC 特异性循环 miRNA 谱，用作儿科 IBD 的诊断生物标志物；2) 评估循环 miRNA 作为儿科 IBD 结果预测因子和替代标志物的效用。血清将从在费城儿童医院儿科 IBD 中心接受内窥镜检查/结肠镜检查疑似 IBD 的患者身上获取。 IBD 特异性 miRNA 将通过微阵列进行鉴定，并在大型独立样本集中进行确认。将使用接受者操作特征分析将循环 miRNA 的诊断潜力与当前 IBD 生物标志物进行比较。将进行纵向研究以确定循环 miRNA 作为替代标记和结果预测因子的效用。除了研究目标外，还制定了全面的培训计划；该计划包括临床研究课程以及研讨会和会议，主题包括生物标志物发现、微阵列分析和专业发展。总体而言，拟议的培训方案平衡地介绍了成为一名成功的独立研究调查员所需的技能和经验，并可能导致儿童 IBD 诊断和临床管理中对侵入性检测的需求大幅减少。