胃癌中钙黏附分子启动子甲基化与幽门螺杆菌感染及肿瘤生物学特性的关系

目的建立甲基化特异性聚合酶链式反应方法检测组织中钙黏附分子（CDH1）的甲基化程度；探索CDH1启动子的甲基化与幽门螺杆菌（HP）感染及与肿瘤分化、浸润、淋巴及远处转移之间的关系。方法采用热转化甲基化特异性聚合酶链式反应法检测2008年1月-2009年12月共40例胃癌手术标本中CDH1的启动子甲基化情况，并回顾性地分析CDH1的启动子甲基化与HP感染、肿瘤分化、浸润、淋巴及远处转移等肿瘤生物学特性的统计学关联。结果胃癌组CDH1基因甲基化阳性率高于对照组（67．5％、12．5％，P〈0．05）。胃癌组中低一未分化肿瘤组CDH1基因甲基化阳性率高于高．中分化肿瘤组（80．6％、22．2％，P〈0．05）；胃癌组中HP阳性患者的CDH1基因甲基化率高于HP阴性患者（78．1％、25．0％，P〈0．05）；而胃癌组中CDH1基因甲基化阳性率与患者性别、肿瘤浸润程度、淋巴转移及远处转移无明显关系（P〉0．05）。结论CDH1基因甲基化可能参与了胃癌的发展过程，并且CDH1基因甲基化可能导致了肿瘤分化程度的降低。CDH1基因甲基化与胃癌患者的HP感染之间可能存在密切关系，提示HP感染可能参与了抑癌基因甲基化失活及肿瘤演变的发展过程。

Research on the Relationship between CDH1 Gene Promoter Hypermethylation and Biological Behavior of Tumor in Human Gastric Carcinoma

Objective To determine the level of CDH1 gene promoter hypermethylation in human gastric carcinoma by establishing MS-PCR method, and analyze retrospectively the possible statistical relationship between CDH1 gene promoter hypermethylation in human gastric carcinoma and HP infection, tumor differentiation, invasion, lymph nodal and distant metastasis, respectively. Methods The bisulfite conversion MS-PCR method was adopted to examine the level of CDH1 gene promoter hypermethylation in 40 cases of human gastric carcinoma tissue collected between January 2008 and December 2009. The statistical relationship between CDH1 gene promoter hypermethylation in human gastric carcinoma and HP infection, tumor differentiation, invasion, lymph nodal and distant metastasis were examined respectively with SPSS statistical tools. Results The positive rate of CDH1 gene promoter hypermethylation in gastric carcinomas （67.5%） was higher than that in paired normal gastric mucosae （12.5%）, and the difference was significant （P 〈 0.05）. In gastric carcinomas, the positive rate of CDH1 gene promoter hypermethylation in well differentiated or moderately differentiated groups （22.2%） was lower than that in poorly differentiated groups （80.6%）, and the difference was significant （P 〈 0.05）. The positive rate of CDH1 gene promoter hypermethylation in HP positive groups （78.1%） was higher than that in HP negative groups （25.0%）, and the difference was significant （P 〈 0.05）. Conclusions CDHl gene promoter hyperrnethylation may play an important role in the process of ttLrnor carcinogenesis in gastric carcinomas. Meanwhile, the CDH1 gene promoter hypermethylation may lead to poor differentiation in gastric carcinomas. CDH1 gene promoter hypermethylation is related to HP infection in the original gastric carcinomas, which shows that HP may get involved in the process of tumor suppressor gene methylation/inactivation and tumor development process.