胃癌组织中PCDH8基因甲基化及Dnmt1表达的关系  

Methylation of the PCDH8 promoter and Dnmt1 expression in gastric cancer

作　　者：于云鹏[1] 李长严[1] 黄冠男[1] 姜相君[1] 

机构地区：[1]青岛市市立医院东院急诊科,青岛266000

出　　处：《中国癌症防治杂志》2014年第3期261-264,共4页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：青岛市科技局科研基金资助项目(2012-1-3-1-(10)-nsh)

摘　　要：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。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.

关 键 词：胃肿瘤 PCDH8基因 DNMT1 基因甲基化 

分 类 号：R735.2[医药卫生—肿瘤]