DC-SIGN/L-SIGN多态性与鼻咽癌易感性关联分析及其功能探索

项目名称： DC-SIGN/L-SIGN多态性与鼻咽癌易感性关联分析及其功能探索

项目编号： No.81460415

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 谢莹

作者单位： 广西医科大学

项目金额： 47万元

中文摘要： 树突状细胞特异性细胞间粘附分子-3结合非整合素因子（DC-SIGN）是人体免疫系统固有的病原识别受体，其相关蛋白L-SIGN特异性表达于肝脏及淋巴细胞表面，与DC-SIGN序列有77%的同源性。二者多态性与多种传染性疾病的易感性相关。鼻咽癌（NPC）是中国南方常见的恶性肿瘤，EB病毒感染上皮细胞是其发病的重要因素之一，有研究显示DC-SIGN有可能是EBV侵入上皮细胞的关键受体，其启动子区多态性与广东地区的鼻咽癌易感性密切相关。我们的前期研究亦提示二者可能存在关联，为进一步深入研究，本课题拟通过病例对照实验，结合EBV感染情况及临床病历资料，在广西地区鼻咽癌人群中开展DC-SIGN及L-SIGN的多态性位点研究，分析其与鼻咽癌易感性的关系，并经生物信息学预测后验证不同区域风险点对该分子功能的影响，为探索EBV感染上皮细胞和鼻咽癌的发病机制及早期预警奠定基础。

中文关键词： C03_鼻咽肿瘤；DC-SIGN；L-SIGN；多态性；关联分析

英文摘要： Dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is an important pathogen recognition receptor on the surface of some subsets of dendritic cell, which plays an important role in innate immune system in human body. DC-SIGN could directly recognize and capture many pathogens in including viruses (HIV-1,Ebola, Cytomegalovirus, et,al) and present them to susceptible cells, facilitating infection of these cells with the pathogens. As a relevant protein, liver/lymph node-specific ICAM-3-grabbing nonintegrin (L-SIGN) which have 77% homology with DC-SIGN may also play an important role in mediating the infection of various viruses. Nasopharyngeal carcinoma（NPC）is the most common malignant tumor in South China. It has been well documented that Epstein-Barr Virus (EBV) infection plays a center role the initiation and development of this tumor, and nearly 100% of the tumor cells are EBV positive. However, the exact mechanism of how EBV infect the nasopharyngeal epithelial cells remain unknown. The participation of DC-SIGN / L-SIGN in mediating virus infection raises the speculation that EBV may infect nasopharyngeal epithelial cells through DC-SIGN/L-SIGN pathway. Recent studies supported this speculation indicating that DC-SIGN may be key receptor for EBV infection in NPC and variations in promoters of DC-SIGN may affect the susceptibility of NPC in the population of Guangdong. However, the relations between DC-SIGN/L-SIGN and EBV infection and NPC occurrence are far from definitive due to limited number of relevant studies. To further investigate the role of DC-SIGN/L-SIGN in NPC, we perform a case-control study, and collect and analyze the materials including EBV status of NPC patients and healthy subjects from the population of Guangxi province. Using bioinformatics and molecular biology methods, the possible genetic variants of DC-SIGN/L-SIGN are selected and the influences of these variations on the function of DC-SIGN/L-SIGN, the NPC susceptibility, EBV status and other clinical characteristics are analyzed and validated. Our results would give a deeper insight into the role of EBV infection in the mechanism of NPC occurrence and improve the effectiveness of its early diagnosis.

英文关键词： nasopharyngeal carcinoma;Dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin;liver/lymph node-specific ICAM-3-grabbing nonintegrin;polymorphism;Correlation analysis