胃癌ERCC1基因甲基化与蛋白表达的关系及其意义

Methylation of the ERCC1 gene and its protein expression in gastric cancer

  • 摘要:
      目的  检测胃癌组织、相应癌旁组织及正常胃组织中ERCC1蛋白表达情况,探讨ERCC1基因启动子CpG岛甲基化与蛋白表达的关系及其意义。
      方法  采用甲基化特异性PCR技术,检测30例胃癌组织、相应癌旁组织、10例正常胃组织中ERCC1基因启动子CpG岛甲基化状态。采用免疫组织化学SP法检测胃癌组织、相应癌旁组织及正常胃组织中ERCC1蛋白的表达情况。
      结果  胃癌组织中ERCC1基因启动子CpG岛完全甲基化率为46.7%(14/30),部分甲基化率为30.0%(9/30),总甲基化率为76.7%(23/30),显著高于相应癌旁组织中该基因的甲基化率13.3%(4/30),差异有统计学意义(P < 0.05)。10例正常胃组织中未检测到该基因的甲基化(0/10)。30例胃癌组织中ERCC1蛋白阴性表达率为70.0%(21/30),显著高于相应癌旁组织中蛋白阴性表达率33.3%(10/30),差异有统计学意义。10例正常胃组织中ERCC1蛋白均阳性表达。胃癌组织中发生ERCC1基因启动子CpG岛甲基化其ERCC1蛋白表达率明显低于胃癌组织中未发生ERCC1基因启动子CpG岛甲基化其ERCC1蛋白表达率。
      结论  ERCC1基因启动子CpG岛甲基化与其蛋白表达呈负相关,ERCC1基因启动子CpG岛甲基化可能是导致其蛋白表达下调的主要原因之一。

     

    Abstract:
      Objective  This study aims to detect the CpG island methylation status of the ERCC1 gene promoter and the expression of the ERCC1 protein in gastric cancer tissues, as well as to investigate the correlation and significance between ERCC1 gene promoter CpG island methylation and protein expression.
      Methods  Methylation-specific PCR was performed to detect the methylation status of the ERCC1 gene in tumor tissues and adjacent cancerous tissues from 30 gastric cancer patients. Ten cases of normal gastric tissues were used as control. Expression of the ERCC1 protein in gastric cancer tissues, adjacent cancerous tissues, and normal gastric tissues was examined by immunohistochemistry S-P method.
      Results  The methylation rate of the ERCC1 gene promoter CpG island in gastric cancer tissues was significantly higher than that in adjacent cancerous tissues (76.7% vs. 13.3%, P < 0.05), and the difference was statistically significant. The incidence of promoter methylation was not found in 10 normal gastric tissues. The negative rate of ERCC1 protein expression in 30 cases of gastric carcinoma tissues was significantly higher than that in adjacent cancerous tissues (70.0% vs. 33.3%, P < 0.05), whereas 10 normal gastric tissues all exhibited positive expression for the ERCC1 protein. The tumor tissues with ERCC1 gene promoter CpG island methylation showed a lower expression of ERCC1 protein than the unmethylated tumor tissues in gastric cancer patients.
      Conclusion  Methylation of the ERCC1 gene promoter CpG island and protein expression are negatively correlated, and methylation of the CpG island of the ERCC1 gene may be one of the main reasons for the down-regulation of protein expression.

     

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