胃癌E-cadherin基因启动子CpG岛甲基化的研究  

CpG Island Methylation of E-cadherin Gene Promoter in Gastric Carcinoma

作　　者：周永宁[1] 徐采朴[2] 韩彪[1] 姬瑞[1] 

机构地区：[1]兰州大学第一医院内镜中心,甘肃兰州730000 [2]第三军医大学西南医院消化内科,重庆400038

出　　处：《癌症》2005年第10期1220-1224,共5页Chinese Journal of Cancer

基　　金：甘肃省科学事业经费(No.QS022-C33-029)~~

摘　　要：背景与目的:目前认为CpG岛甲基化导致转录抑制是恶性肿瘤发生的重要机制之一。E-cadherin能抑制肿瘤细胞的浸润和转移,被公认为是浸润、转移抑制基因。低分化胃癌常表现有E-cadherin基因失活。我们通过检测胃癌及癌旁组织中E-cadherin基因启动子CpG岛甲基化水平,初步探讨胃癌的发病机制。方法:采用特异性甲基化PCR(MSP)法检测51例胃癌组织及37例癌旁组织中的E-cadherin基因启动子CpG岛甲基化水平,采用免疫组织化学染色法检测E-cadherin表达。结果:健康对照组织中未检测到CpG岛甲基化,4例(10.8%)癌旁组织检测到CpG岛甲基化,32例(62.7%)胃癌组织中检测到CpG岛甲基化。低分化腺癌(72.2%,26/36)CpG岛甲基化显著高于高分化腺癌(33.3%,6/15)(P<0.01),T1/T2期(55.6%,10/18)与T3/T4期胃癌(66.7%,22/33)的CpG岛甲基化率无显著性差异(P>0.05)。32例CpG岛甲基化胃癌中27例(84.5%)E-cadherin表达下调,19例非甲基化胃癌中5例(26.3%)E-cadherin表达下调。未发现E-cadherin基因CpG岛甲基化与幽门螺杆菌感染有关。结论:胃癌、尤其是低分化腺癌广泛存在E-cadherin基因启动子CpG岛甲基化,启动子CpG岛甲基化可能参与胃癌的早期过程,E-cadherin基因CpG岛甲基化与幽门螺杆菌感染无相关关系。BACKGROUND ＆ OBJECTIVE： Transcriptional silencing by CpG island methylation is now believed to be an important mechanism of carcinogenesis. E-cadherin can suppress tumor cell invasion and metastasis, and is considered as an invasion/metastasis suppressor gene. Inactivation of E-cadherin gene often occurs in poorly differentiated gastric carcinoma. This study was to investigate the CpG island methylation status of E-cadherin gene promoter in primary human gastric carcinomas and adjacent gastric tissues, and to explore the mechanism of gastric carcinogenesis. METHODS： The CpG island methylation status of E-cadherin gene promoter in 51 specimens of primary human gastric carcinoma, 37 specimens of adjacent gastric tissue, and 12 specimens of normal gastric mucosa was detected by methylation-specific polymerase chain reaction （MSP）. The expression of E-cadherin was evaluated by immunohistochemistry. RESULTS：The CpG island methylaion was not detected in normal gastric mucosa, but detected in 32 （62.7%） gastric carcinoma specimens and 4 （10.8%） adjacent gastric specimens. It occurred more frequently in poorly differentiated carcinomas than in well differentiated carcinomas [72.2% （26/36） vs. 33.3% （6/15）, P〈 0.01], and it was presented at similar rates in stage T1/T2 carcinomas and stage T3/T4 carcinomas [55.6% （10/18） and 66.7% （22/33）, P〉0.05]. Down-regulation of E-cadherin expression was detected in 84.5% （27/32） tumor tissues with methylated CpG island and 26.3% （5/19） tumor tissues with unmethylated CpG island. No statistical correlation was found between CpG island methylaion and Helicobacter pylori infection. CONCLUSIONS： The CpG island methylaion of E-cadherin gene promoter commonly exists in gastric carcinoma, particularly in poorly differentiated adenocarcinoma. E-cadherin promoter methylation may be involved in the early process of gastric carcinogenesis, but has no correlation to Helicobacter pylori infection.

关 键 词：胃肿瘤 E-CADHERIN CPG岛甲基化 幽门螺杆菌 

分 类 号：R735.2[医药卫生—肿瘤]