肺腺癌HOXA10基因启动子甲基化的改变及其临床意义

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。

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

Objective To investigate the methylation status of promoter of HOXA10 gene in lung adenocarcinoma and its cor-relation 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 re-lationship between the hypomethylation status and clinicopathologic features, prognosis was analyzed. Results MSP test indicated that 17 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). Anal-ysis 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 HOXA10 meth-ylation( 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.