miR-34启动子甲基化在胃癌发病过程中的作用研究

The role of miR-34 promoter methylation in the pathogenesis of gastric cancer

目的探讨胃癌组织中miR-34基因启动子甲基化状态对miR-34的表达影响及其与患者预后的相关性。方法采用实时荧光定量PCR法检测50例胃癌组织及癌旁组织中成熟miR-34的表达。采用甲基化特异性PCR法检测miR-34基因启动子的甲基化状态,运用统计学分析miR-34基因启动子甲基化状态与miR-34表达量之间的关系,并随访患者复发和转移情况。结果胃癌组织中成熟miR-34的表达水平比癌旁组织明显降低(P<0.05)。miR-34甲基化水平与淋巴结转移有相关性(P<0.05)。miR-34基因启动子非甲基化组的成熟miR-34表达水平明显高于甲基化阳性单一模式组和甲基化阳性混合模式组(P<0.05)。与非甲基化组和甲基化阳性混合模式组相比,miR-34基因甲基化阳性组的胃癌患者复发和转移率明显升高(P<0.05)。结论在胃癌患者中,miR-34基因启动子甲基化可导致miR-34表达下调。miR-34基因启动子的甲基化状态与胃癌的复发与转移明显相关。

Objective To investigate the effect of miR-34 gene promoter methylation status on the expression of miR-34 in gastric cancer and its correlation with prognosis. Methods The expression of mature miR-34 in 50 gastric cancer tissues and adjacent tissues was detected by real-time fluorescent quantitative PCR. The methylation status of the miR-34 gene promoter was detected by methylation-specific PCR. The relationship between miR-34 gene promoter methylation status and miR-34 expression was analyzed and the patients were followed up for recurrence and metastasis. Results The expression of mature miR-34 in gastric cancer tissues was significantly lower than that in the control group(P<0.05). miR-34 expression was correlated with lymph node metastasis (P<0.05). The expression level of mature miR-34 in non-methylated group was significantly higher than that in methylated positive single mode group and methylated positive mixed mode group(all P<0.05). Compared with non-methylated group and methylated positive mixed group,the recurrence and metastasis rate of gastric cancer patients with miR-34 methylation positive were significantly higher(P<0.05). Conclusion Methylation of miR-34 gene may lead to the down-regulation of miR-34 expression in some gastric cancer patients. The methylation status of miR-34 is associated with the recurrence and metastasis rate of gastric cancer.