非小细胞肺癌患者血浆DAPK基因甲基化检测及其临床意义

Detection and Clinical Significance of DAPK Gene Methylation in Plasma of Non-small Cell Lung Cancer Patients

目的分析非小细胞肺癌(NSCLC)患者血浆中死亡相关蛋白激酶(DAPK)基因异常甲基化及其在NSCLC筛查和诊断方面的临床意义。方法用巢式甲基化特异性聚合酶链反应(nMSP)检测112例NSCLC患者癌组织、癌旁组织、外周血血浆和112例正常对照组血浆样品中DAPK基因的甲基化情况,并比较各组检测结果。结果癌组织DAPK基因甲基化率为59.8%,高于癌旁组织的8.0%(P<0.001),其中鳞癌、腺癌、腺鳞癌癌组织和癌旁组织间的甲基化检出率比较差异均有统计学意义(P<0.001);NSCLC患者血浆中DAPK基因甲基化检测率为21.4%,对照组血浆未检测到DAPK基因甲基化(P<0.001)。血浆中DAPK基因甲基化检出率与NSCLC临床分类、临床分期和病理类型无明显相关性。结论利用nMSP法对血浆样本DAPK基因甲基化检测可为非小细胞肺癌的筛查和诊断提供有价值的信息。

Objective To detect the methylation status of the death associated protein kinase（DAPK） gene in the plasma of non-small cell lung cancer（NSCLC） patients,and to evaluate its clinical significance in screening and early diagnosis of NSCLC.Methods 112 cases of NSCLC patients and corresponding control cases were enrolled,by using nested methylation-specific polymerase chain reaction（nMSP）,we determined the methylation status of the DAPK gene in the lung cancer tissues,adjacent tissues,plasma from peripheral blood and 112 normal control blood samples.The result of each group was compared.Results The total frequency of the DAPK gene methylation was 59.8% in NSCLC tissues,significantly higher than that in the adjacent tissues at 8.0%（P〈0.001）.Compared to adjacent tissues groups,the hypermethylation frequency in the lung cancer tissues exhibited significant difference in squamous cell carcinoma,adenocarcinoma and adenosquamous carcinoma（P〈0.001）.The hypermethylation frequency for DAPK gene was 21.4% in the plasma of the 112 NSCLC cases,without positive result in the plasma of the control group（P〈0.001）.The hypermethylation frequency in plasma did not significantly correlate to the clinical classification,pathologic type and clinical staging of the NSCLC.Conclusion Detection of the DAPK gene methylation in the plasma of NSCLC patients may provide valuable information for early screening and diagnosis of the NSCLC.