【摘要】 目的探讨人切除修复交叉互补基因1(excision repair cross-complementing gene 1,ERCC1)基因启动子Cp G岛甲基化和DNA甲基转移酶1(DNA methyltransferase 1,DNMT1)基因的表达与胃癌发生的关系及临床意义。方法采用甲基化特异性PCR(MSP)技术检测60例胃癌组织及其相应癌旁正常组织中ERCC1基因启动子区甲基化状态。同时应用逆转录聚合酶链反应(realtime RT-PCR)法和免疫组化(IHC)SP法分别检测ERCC1及DNMT1基因的mRNA和蛋白表达水平。结果胃癌组织中ERCC1基因启动子Cp G岛甲基化阳性率为68.3%,明显高于相应的癌旁正常组织(23.3%)。胃癌组织中ERCC1 mRNA阳性率显著低于癌旁正常组织(31.7%vs 71.7%,P<0.05),而胃癌组织中DNMT1 mRNA阳性率明显增高,差异均有统计学意义(78.3%vs 16.7%,P<0.05)。ERCC1 mRNA阴性表达的胃癌组织中基因启动子的甲基化率较ERCC1 mRNA阳性表达者明显升高,差异具有统计学意义(92.7%vs 15.8%,P<0.001)。结论 ERCC1基因启动子Cp G岛高甲基化及DNMT1基因表达上调可能参与胃癌的发生与发展。DNMT1可能调控ERCC1基因的甲基化。更多还原

【Abstract】 Objective To investigate promoter methylation of ERCC1 gene,expression of DNMT1 and the relationship between expression of DNMT1 and gastric cancer. Methods Methylation status of the ERCC1 gene in 60 gastric cancer tissues and 60 normal tissues adjacent to cancer were detected by methylation-specific PCR( MSP). RT-PCR was used to detect the mRNA expressions of ERCC1 and DNMT1,immunohistochemistry( IHC) was employed to detect the protein expressions of ERCC1 and DNMT1 in the above samples. Results The positive rate of promoter methylation of the ERCC1 in gastric cancer was 68. 3%,higher than that in normal tissues adjacent to cancer( 23. 3%,P < 0. 001).The positive rate of ERCC1 expression in gastric cancer was significantly lower than that in normal tissues adjacent to cancer( 31. 7% vs 71. 7%,P < 0. 05). DNMT1 mRNA expression was higher compared with normal tissues adjacent to cancer( 78. 3% vs 16. 7%,P < 0. 05). Methylation rate of ERCC1 mRNA negative expression in gastric cancer was significantly higher than that of ERCC1 mRNA positive expresion in gastric cancer( 92. 7% vs 15. 8%,P < 0. 001). Conclusion The promoter methylation of the ERCC1 gene and high expression of DNMT1 may be associated with the occurrence of gastric cancer.更多还原