Barrett's esophagus early detection project

巴雷特食管早期检测项目

• 批准号: 10702959
• 负责人: Christian Abnet
• 金额: $ 7.47万
• 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/10702959
• 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; Esophagus; Gastroesophageal reflux disease; Genetic Polymorphism; Genetic Transcription; Germ Lines; Goals; Hormones; Laboratories; Medical center; Patients; Pattern; Periodicity; 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 archive; 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.

该项目的目的是确定一个实用的基于血液的生物标志物，该标志物可以用作筛查测试，以确定谁患有巴雷特的食管（BE），而谁没有。该项目的次要目标是表征与BE相关的生殖系和组织生物标志物，并比较有或没有GERD的非BEB患者的生物标志物。三级目标是探索血液或组织中生物标志物之间的关联，并从BE发育不良或EAC进行进展，并评估随着时间的推移蛋白质组学模式的稳定性。这项研究将在1992年在贝塞斯达国家海军医疗中心（NNMC）建立的巴雷特食管注册中心（目前为206名注册人）的患者中进行，以及其他条件的GI Clinic在NNMC的GI Clinic的大约600例非匹配的非本镜患者的比较组。将收集血液和组织样本以及有关危险因素和药物以及GERD的问卷数据。数据分析将主要基于对新收集的食管活检，刷样品和血液样本的实验室测试，但其次还包括使用档案活检样品。注册患者的随访将包括标准的周期性监测内窥镜，其他血液样本和确定疾病状态（即进展）。为了区分BE与非患者，我们将：（i）评估血清蛋白质组学模式的状态的可预测性； （ii）表征食道活检和刷样品，以选择选定的DNA改变，RNA表达和蛋白质组学特征； （iii）可能与BE相关的选定多态性的基因型患者； （iv）比较有或没有GERD的非贝生患者的血液和组织生物标志物； （v）探索生物标志物与从BE发育不良或EAC的发展的关联； （vi）评估患者的蛋白质组学模式稳定性。 该项目的最新研究对BE，Cardia和正常鳞状组织的组织RNA表达差异（i）进行了（i）； （ii）在情况下比较血清激素与非案例； （ii）在病例和非案例中对血清蛋白质组学进行了试点研究。