食管鳞癌异质性及耐药机制的多组学贯穿分析研究

项目名称： 食管鳞癌异质性及耐药机制的多组学贯穿分析研究

项目编号： No.81330063

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 崔永萍

作者单位： 山西医科大学

项目金额： 290万元

中文摘要： 食管癌在我国癌症死亡率中列第四，化疗耐药是导致治疗失败的主要原因，阐明耐药机制是目前临床治疗的关键突破口。近年组学研究表明，复杂的肿瘤异质性是肿瘤治疗耐受的重要原因，迫切需求从肿瘤基因组进化角度、多水平、多层次探讨肿瘤发生发展中耐药机理。前期我们完成了20例食管癌全基因组、100例外显子组、96例目标区域捕获深度测序以及5个食管癌敏感/耐药细胞系基因表达谱、小RNA测序，绘制了食管癌基因组图谱、食管癌相关基因变异图谱和耐药相关图谱。本项目拟在此基础上，通过多组学贯穿研究策略，整合分析并补充验证食管癌患者及细胞系耐药相关遗传变异及调控网络，从基因、信号调控网络等多级水平，从分子、细胞和生物体等多层次，从动态、整体角度对食管癌发生发展相关的耐药分子机制进行系统研究，鉴定食管癌耐药特异性标记，开发食管癌耐药分型的分子标记用于指导临床用药，为解决食管癌耐药问题、筛选理想的联合抗癌药物提供候选靶标。

中文关键词： C06_食管肿瘤;异质性;耐药;高通量测序;多组学分析

英文摘要： Esophageal squamous cell carcinoma (ESCC) is the forth most common cancer in China. From the viewpoint of cancer treatment, the key reason for chemotherapy failure is resistance to anticancer drugs, which promotes us to fully understand the mechanism of chemoresistance to improve the chemotherapeutic effect. The recent data derived from high throughput analyses have showed that tumor heterogeneity contributed to chemoresistance. It is a matter of urgency to illuminate the chemoresistant-related genome variations in considering the clonal evolution of cancer development at the multiple-omics levels. Previously, we sequenced and analyzed the whole genomes of 20 ESCC cases, the whole exomes of 100 ESCC cases, the target captures of 96 ESCC cases, and the digital gene expression, small RNA profiling of five chemotherapeutics-sensitive or -resistant esophageal cancer cell lines. Statistical analyses yield a comprehensive map of genomic abnormalities and chemoresistant-related changes in ESCC. Based on our previous work, we will integrate the genomic data, transcriptomic data, and target region capture data of ESCC patients with digital expression profiling, small-RNA data, DNA methylation data of esophageal cancer cell lines to validate the chemoresistant-related genes and its relevant regulatory networks through omics analyses strategy. The goal of this project is to deepen understanding the dynamic chemoresistant melocular mechanism during the development of ESCC at multiple-level, thus allow the identification of suitable therapeutic targets and diagnostic/prognostic biomarkers, might represent a strategy for the selection and prioritization of potential biomarkers and their translation into practical use.

英文关键词： ESCC;heterogeneity;chemoresistance;high throughput sequence;omics analyses strategy