Barretts esophagus early detection project

Barretts食管早期检测项目

• 批准号: 9339197
• 负责人: Philip Taylor
• 金额: $ 11.82万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9339197
• 关键词: Barrett Esophagus; Biological Markers; Biopsy; Biopsy Specimen; Blood; Blood specimen; Clinic; DNA Sequence Alteration; Data; Data Analyses; Disease; Dysplasia; Early Diagnosis; Endoscopes; Endoscopy; Esophageal; Gastroesophageal reflux disease; Genetic Polymorphism; Genetic Transcription; Germ Lines; Goals; Hormones; Laboratories; Medical center; Patients; Pattern; Pharmaceutical Preparations; Pilot Projects; Proteomics; Questionnaires; Registries; Risk Factors; Sampling; Serum; Study of serum; Testing; Time; Tissue Sample; Tissues; base; blood-based biomarker; comparison group; follow-up; genotyped patients; patient registry; screening; stomach cardia; tissue biomarkers

The goal of this project is to identify a practical blood-based biomarker(s) that can be used as a screening test to determine who has Barrett's esophagus (BE) and who does not. Secondary goals of the project are to characterize germ line and tissue biomarkers associated with BE, and compare biomarkers in non-BE patients with and without GERD. Tertiary goals are to explore associations between biomarkers in blood or tissue and progression from BE to dysplasia or EAC, and to assess the stability of proteomic patterns over time. This study will be conducted among patients in the Barrett's Esophagus Registry (currently with 206 registrants) established at the National Naval Medical Center (NNMC) in Bethesda beginning in 1992 as well as a comparison group of approximately 600 matched non-BE patients endoscoped in the GI clinic at NNMC for other conditions. Blood and tissue samples will be collected as well as questionnaire data on risk factors and medications as well as GERD. Data analyses will be based primarily on laboratory testing of newly collected esophageal biopsies, brush samples, and blood samples, but secondarily will also include use of archival tissue biopsy samples. Follow-up of BE Registry patients will include standard periodic surveillance endoscopies, additional blood samples, and ascertainment of disease status (i.e., progression). To distinguish BE versus non-BE patients, we will: (i) assess predictability of BE status from serum proteomic patterns; (ii) characterize esophageal biopsies and brush samples for selected DNA alterations, RNA expression, and proteomic profiles; (iii) genotype patients for selected polymorphisms potentially associated with BE; (iv) compare blood and tissue biomarkers in non-BE patients with and without GERD; (v) explore the association of biomarkers with progression from BE to dysplasia or EAC; and (vi) assess proteomic pattern stability over time in BE patients. Recent studies in this project have (i) profiled and compared tissue RNA expression differences among BE, cardia, and normal squamous tissues in BE cases; (ii) compared serum hormones in BE cases versus noncases; and (ii) conducted a pilot study of serum proteomics in BE cases and noncases.

该项目的目标是确定一种实用的血液生物标志物，可用作筛查测试来确定谁患有巴雷特食管 (BE)，谁没有。该项目的次要目标是表征与 BE 相关的种系和组织生物标志物，并比较患有和不患有 GERD 的非 BE 患者的生物标志物。第三个目标是探索血液或组织中的生物标志物与从 BE 到发育不良或 EAC 的进展之间的关联，并评估蛋白质组模式随时间的稳定性。这项研究将在贝塞斯达国家海军医疗中心 (NNMC) 于 1992 年开始建立的 Barrett 食管登记处（目前有 206 名登记者）的患者中进行，对照组中约 600 名在该中心接受内窥镜检查的匹配非 BE 患者。 NNMC 胃肠道诊所治疗其他病症。将收集血液和组织样本以及有关危险因素和药物以及胃食管反流病的问卷数据。数据分析将主要基于对新收集的食管活检、刷检样本和血液样本的实验室测试，但其次也将包括使用档案组织活检样本。 BE 登记患者的随访将包括标准定期监测内窥镜检查、额外的血液样本和确定疾病状态（即进展）。为了区分 BE 与非 BE 患者，我们将： (i) 根据血清蛋白质组模式评估 BE 状态的可预测性； (ii) 表征食管活检和刷检样本的选定 DNA 改变、RNA 表达和蛋白质组谱； (iii) 对患者进行可能与 BE 相关的选定多态性的基因分型； (iv) 比较患有和不患有 GERD 的非 BE 患者的血液和组织生物标志物； (v) 探索生物标志物与从 BE 发展为不典型增生或 EAC 的关联； (vi) 评估 BE 患者随时间推移的蛋白质组模式稳定性。 该项目最近的研究 (i) 分析并比较了 BE 病例中 BE、贲门组织和正常鳞状组织之间的组织 RNA 表达差异； (ii) 比较 BE 病例与非病例的血清激素； (ii) 对 BE 病例和非病例的血清蛋白质组学进行了初步研究。