肺腺癌HOXA10基因启动子甲基化的改变及其临床意义

The promoter hypomethylation of HOXA10 gene in lung adenocarcinoma and its clinical significance

目的探讨肺腺癌HOXA10基因启动子区甲基化改变情况及其与临床病理特征和预后的关系。方法采用甲基化特异性聚合酶链反应(MSP)法检测30例肺腺癌标本及其配对癌旁组织标本中HOXA10基因启动子甲基化状态,并分析HOXA10基因甲基化状态与临床病理特征和预后的关系。结果 MSP法检出17例(56.7%)肺腺癌组织HOXA10基因启动子区发生低甲基化改变,其中4例为完全去甲基化改变;而癌旁组织仅有6例(20.0%)HOXA10基因启动子区发生低甲基化改变(P<0.05)。HOXA10低甲基化与肿瘤大小、临床分期及淋巴转移有关(P<0.05),而与性别、年龄、肿瘤分化程度无关(P>0.05)。生存分析显示,HOXA10基因低甲基化患者的中位无病生存期为27.0个月,明显低于HOXA10基因甲基化患者的46.0个月(P=0.002)。结论肺腺癌HOXA10基因启动子区低甲基化为频发事件,提示与患者的不良预后有关,可作为判断肺腺癌预后的指标。

Objective To investigate the methylation status of promoter of HOXA10 gene in lung adenocarcinoma and its correlation with clinicopathologic characteristics and prognosis. Methods Methylation-specific polymerase chain reaction（ MSP） was used to examine the promoter hypomethylation in 30 lung adenocarcinoma samples and their corresponding lung normal tissues. The relationship between the hypomethylation status and clinicopathologic features,prognosis was analyzed. Results MSP test indicated that17 cases（ 56. 7%） of 30 lung adenocarcinoma samples showed hypomethylation of HOXA10 promoter,and 4 cases were even complete demethylation. But only 6 cases（ 20. 0%） of 30 corresponding lung normal tissues showed promoter hypomethylation（ P〈 0. 05）. Analysis revealed that the frequency of hypomethylation was correlated with size of tumor,clinical stage and lymph node metastasis（ P 〈0. 05）,but not with age,gender and tumor differentiation（ P〉 0. 05）. Statistical analysis showed that the median disease-free survival of patients with HOXA10 hypomethylation was 27. 0 months,which was significantly lower than 46. 0 months of those with HOXA10methylation（ P = 0. 002）. Conclusion HOXA10 gene promoter hypomethylation is a frequent epigenetic event in lung adenocarcinoma,which indicates poor prognosis of patients. It may be a biological marker to predict the prognosis for lung adenocarcinoma.