食管癌高发区人群癌前病变的外周血中miRNAs筛查标志物研究

项目名称： 食管癌高发区人群癌前病变的外周血中miRNAs筛查标志物研究

项目编号： No.81473056

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘芬

作者单位： 首都医科大学

项目金额： 70万元

中文摘要： 食管癌早期发现是其防治研究中的瓶颈问题。研究表明，外周血中miRNAs的差异表达与肿瘤发生风险相关。本课题组前期研究发现食管癌与其癌旁组织间有38个显著差异表达的miRNAs，这些差异表达的miRNAs在食管癌和癌前病变的外周血中的特异性及其在食管癌发生中的生物学功能，目前尚不清楚。本研究拟采用人群为基础的病例对照研究设计，用qRT-PCR技术盲法验证食管癌、异型增生和健康对照人群外周血中候选miRNAs的表达水平，探讨其与食管癌及癌前病变的关联；用Logistic回归构建筛检模型，ROC曲线评价模型的诊断价值；采用回顾性队列研究验证模型的外部真实性；并与血清中CEA、CA19-9、SCCA比较筛检效率；用生物信息学方法预测靶基因，最后从组织和细胞水平深入探讨特异miRNAs在食管癌发生中的作用机制。旨为食管癌早期筛查和人群筛查技术优化及预防效果评价的中间肿瘤标志物等研究提供科学依据。

中文关键词： 食管癌；癌前病变；生物标志物；筛查；微小RNA

英文摘要： Esophageal squamous cell carcinoma (ESCC) is a complex and malignant tumor, and is one of the major cancers threatening human health. The early detection is critical for the cancer treatment and the patient survival. Circulating miRNAs is very stable and shows relatively specific expression profile in different diseases, it has potential to serve as a new kind of screening biomarker for ESCC. In the previous study, we have found the different expression panel for miRNAs in the ESCC tissue and adjacent tissue; in this project, the candidate miRNAs were validated blindly in the plasma of ESCC, dysplasia and healthy population by qRT-PCR at a case-control and a cohort study in ESCC high-risk area. Logistic regression model was used to estimate the parameters, and ROC curve was used to assess the accuracy of the miRNAs panel model. Meanwhile, we will compare the diagnosis accuracy of miRNAs panel to the other serum biomarkers, such as CEA、CA19-9、SCCA. At last, we will also conduct functional analyses by means of specialized algorithms, molecular biology techniques, and cell experiment to dissect its roles and regulatory networks in esophageal carcinogenesis. We intend to provide both early screening and prevention evidences for understanding the plasma miRNAs, as a biomarker of ESCC.

英文关键词： Esophageal cancer;Precancerous lesions;Biomaker;Screening;miRNAs