胃癌BRCA1基因甲基化及蛋白表达的检测及意义

摘要

目的：通过胃癌BRCA1基因启动子CpG岛甲基化状态及BRCA1蛋白表达的检测，探讨BRCA1基因启动子CpG岛甲基化与BRCA1蛋白表达的相关性及其意义。方法采用甲基化特异性PCR技术（MSP）检测胃癌组织及癌旁组织基因甲基化状态，采用免疫组化SP法检测蛋白表达情况。结果①胃癌组织中BRCA1基因启动子CpG岛完全甲基化率为16．2％（6／37），部分甲基化率为32．4％（12／37），总甲基化率为48．6％，癌旁组织中BRCA1基因启动子CpG岛总甲基化率为5．4％（2／37）。胃癌组织中BRCA1基因启动子CpG岛总甲基化率显著高于对应癌旁组织（P＜0．05）。6例正常胃组织中均未检测到该基因的甲基化。②37例胃癌组织中BRCA1蛋白阳性表达率为37．8％（14／37），显著低于癌旁组织中BRCA1蛋白阳性表达率70．3％（26／37），差异有统计学意义（P＜0．05）。6例正常胃组织中BRCA1蛋白均阳性表达。 BRCA1基因启动子CpG岛甲基化与BRCA1蛋白表达呈负相关。结论胃癌组织中存在高比例的BRCA1基因启动子CpG岛甲基化， BRCA1基因启动子CpG岛甲基化与BRCA1蛋白表达呈负相关，BRCA1基因启动子CpG岛甲基化可能是导致BRCA1蛋白表达缺失的主要原因之一。%Objective To detect the methylation of CpG island in the promoter region of BRCA 1 gene and the level of BRCA1 protein in gastric cancer tissues , and to investigate the relationship between the methylation of CpG island in the promoter region of BRCA1 gene and BRCA1 protein level and its significance .Methods The methylation of CpG is-land in the promoter region of BRCA 1 gene was determined by methylation -specific polymerase chain reaction ( MSP) . The levels of BRCA1 were examined by immunohistochemistry S -P method.Results ① The total methylation rate of CpG island in the promoter region of BRCA1 gene was 48.6%(18/37) in gastric cancer tissues, which was significantly higher than 5.4%(2/37) in adjacent non -cancerous tissues (P<0.05).The methylation of the CpG island was not found in 6 normal gastric tissues .② The methylation rate of CpG island in the promoter region of BRCA 1 gene was 37.8%(14/37) in gastric cancer tissues, which was significantly lower than 70.3%(26/37) in adjacent non -cancer-ous tissues (P<0.05).The expression of BRCA1 protein was detected in 6 normal gastric tissues.③According to the Spearman's correlation analysis , the methylation of CpG island in the promoter region of BRCA 1 gene and BRCA1 protein expression was negatively correlated .Conclusions A high proportion of CpG island in the promoter region of BRCA 1 gene is methylated in gastric cancer tissues .The methylation of CpG island in the promoter region of BRCA 1 gene is neg-atively correlated with BRCA 1 protein level .The methylation of the CpG island may be an important reason for the loss of BRCA1 protein expression .