胃癌组织中PCDH8基因甲基化及Dnmt1表达的关系

目的 探讨PCDH8（protocadherin 8）基因在人胃癌组织中的甲基化状态及其与甲基转移酶1（Dnmt1）表达之间的关系,分析其与胃癌发生、发展的关系。方法 取60例手术切除的胃癌组织及其相应癌旁正常胃黏膜组织（距癌组织5 cm以上）,以甲基化特异性聚合酶链式反应（methylationspecific PCR,MSP）检测60例胃癌组织及其癌旁正常胃黏膜组织中PCDH8基因启动子区甲基化的状态;以免疫组化SP法分别检测PCDH8基因蛋白及Dnmt1蛋白的表达水平。结果 胃癌组织中PCDH8甲基化率为55.0%（33/60）,癌旁正常胃黏膜组织中PCDH8的甲基化率为3.3%（2/60）,两者比较差异有统计学意义（χ2=38.76,P〈0.001）,PCDH8甲基化的发生率与患者年龄、性别及TNM分期等差异均无统计学意义（P均〉0.05）,而与有无淋巴结转移的差异有统计学意义（χ2=17.47,P〈0.001）。PCDH8蛋白在癌旁正常胃黏膜组织中的表达（90.0%）明显高于胃癌组织（11.7%）（χ2=73.65,P〈0.001）,Dnmt1蛋白在胃癌组织中的阳性表达率（73.3%）明显高于癌旁正常胃黏膜组织的表达率（5.0%）（χ2=58.79,P〈0.001）。胃癌组织中PCDH8蛋白与Dnmt1蛋白的表达呈负相关（r=-0.544,P〈0.001）。结论PCDH8基因甲基化及Dnmt1的高表达可能参与了胃癌的发生和发展。

Methylation of the PCDH8 promoter and Dnmtl expression in gastric cancer

Objective To investigate the relationship of gastric carcinogenesis to promoter methylation and expression of the Proto-cadherin-8 （PCDH8）gene,as well as to expression of Dnmt1 protein. Method Samples of cancerous and normal gastric mucosa were obtained surgically from 60 patients with primary gastric cancer. Methylation-specific PCR was used to determine the methylation status of the PCDH8 promoter,while immunohistochemistry was used to measure levels of PCDH8 and Dnmt1 proteins. Results Among the 60 patients,33（55.0%）showed a methylated PCDH8 promoter in samples of cancerous tissue,compared to only 2（3.3%）who showed a methylated promoter in normal samples （χ2=38.76,P〈0.001）.Methylation status of the PCDH8 promoter showed no significant association with patient age,sex,or TNM stage;methylation was,however,associated with lymph node metastasis （χ27.47,P〈0.001）. Gastric cancer tissue showed significantly lower levels of PCDH8 protein than normal tissue （11.7% vs 90.0%,χ2=73.65,P〈0.001） and significantly higher levels of Dnmt1 protein （73.3% vs 5.0%,χ2=58.79,P〈0.001）.In gastric cancer samples,the level of PCDH8 protein correlated negatively with that of Dnmt1 protein （r=-0.544,P〈0.001）. Conclusion Methylation of the PCDH8 promoter and elevated expression of Dnmt1 may be associated with the occurrence of gastric cancer.