MHC区域基因在食管癌变中的作用机制研究

Esophageal cancer (EC) was one of the most common malignant tumor in the world. At present, the factor responsible for initiating the response of esophageal carcinogenesis is unknown in the MHC region. Based on the analysis of our previous GWAS from 25,000 case and normal control subject and the SNPs from the MHC region, the MHC region may confer impotant risk loci for EC, but without further fine mapping. Thus, the aim of this study is to validate these 24 promising SNPs by strict quality control in the MHC region (PLoS One, 2014) on the cases (n=1000) and normal control (n=1000) by Sequenom technique, and to identify the risk SNPs and loci in the MHC region for EC. Simultaneously, RT-PCR, Western blotting and immunohistochemical were applied to explore the protein expression pattern of the related genes in human EC, precancerous and adjacent normal tissues, and to observe the effects of cell biological characteristics of related genes in EC cell line. This study is a continuation and deeper of our previous research ideas. This study will provide the theoretical and experimental basis on the EC to screen, prevent and treat through demonstrating the molecular mechanism of the MHC region genes in esophageal carcinogenesis.

食管癌是世界上最常见的恶性肿瘤之一，目前关于激发MHC区域食管癌变的反应机制不清。本研究组在前期工作中对2.5万例食管癌（EC）和对照组GWAS研究及MHC区域SNPs分析发现，MHC区域和食管癌发生有重要关系，但没有进行进一步的研究。因此，本研究旨在采用Sequenom分型技术，对通过质量控制的24个SNPs位点（PLoS One，2014）在1000例病例组和1000例对照组中进行验证，确定MHC区域与EC相关的遗传易感SNPs位点；同时利用RT-PCR、Western Blot和免疫组化等技术，探讨MHC区域食管癌相关蛋白在人食管癌组织，各级癌前病变和正常上皮组织中的表达及该基因对食管癌细胞生物学特性的影响。本项目是我们前期研究思路的延续和深入，初步揭示了MHC区域基因在食管癌变中的作用机制，为高危人群筛查、个体预防及治疗提供一定的理论及实验依据。

食管癌是世界上最常见的恶性肿瘤之一，目前关于激发MHC区域食管癌变的反应机制不清。本研究组在前期工作中对2.5万例食管癌（EC）和对照组GWAS研究及MHC区域SNPs分析发现，MHC区域和食管癌发生有重要关系，但没有进行进一步的研究。因此，本研究采用TagMan分型技术，对通过质量控制的5个SNPs位点在2026例病例组和2384例对照组中进行验证，确定MHC区域与EC相关的遗传易感SNPs位点；同时利用qRT-PCR、Western Blot和免疫组化等技术，探讨MHC区域食管癌相关蛋白HLA-DQA1在人食管癌组织和正常上皮组织中的表达及该基因对食管癌患者预后的影响。本项目是我们前期研究思路的延续和深入，本项目的完成揭示了MHC区域基因在食管癌变中的作用机制，为高危人群筛查、个体预防及治疗提供一定的理论及实验依据。