E-钙粘蛋白基因甲基化在胃癌发展中的机制研究

Study on the mechanism of E-cadherin gene methylation in the process of gastric cancer

目的检测癌前病变和不同分化阶段胃癌中E-cadherin基因甲基化状态、mRNA和其蛋白表达情况。方法应用甲基化特异性PCR(methylation-specific PCR,MSP)分析、原位杂交和免疫组化等方法进行研究。结果癌前病变组织中E-cadherin DNA甲基化阳性表达率高于正常胃黏膜组织,差异有统计学意义(P<0.05);E-cadherin mRNA在正常胃黏膜中的表达高于癌前病变组织,差异有统计学意义(P<0.05);E-cadherin蛋白表达在正常胃黏膜中的表达高于癌前病变组织,差异有统计学意义(P<0.05)。E-cadherin DNA甲基化、E-cadherin mRNA及E-cadherin蛋白均与胃癌的分化程度相关。结论 E-cadherin基因高甲基化可能引起E-cadherin mRNA和蛋白表达减低,使其失去细胞粘附作用,从而增加了胃癌恶变的风险。

Objective To detect methylation, mRNA and protein expression of E - cadherin gene in precancerous lesions and different stages of gastric cancer. Methods Methylation - specific PCR（MSP） , in situ hybridization and immunohistochemistry were used respectively. Results The positive rate of express of E - cadherin DNA methylation in precancerous lesions were significantly higher than in normal gastric mucosa, the difference had statistical significance （ P 〈 0.05 ） ; E - cadherin mRNA expression in normal gastric mucosa were significantly higher than in precancerous lesions, and the difference had statistical significance（ P 〈 0.05 ） ; E - eadherin protein expression in normal gastric mucosa were significantly higher than in precancerous lesions, and the difference had statistical significance（ P 〈 0.05 ）. Methylation status, mRNA and protein of E -cadherin DNA were significantly correlated with the differentiation of gastric cancer. Conclusion E - cadherin gene hypermethylation may decrease mRNA and protein expression, which would lead to the loss of cell adhesion, and therefore, it will increase the risk of malignant transformation of gastric cancer.