痰标本p16和MGMT基因甲基化对肺癌的诊断价值

目的：分析肺癌患者痰标本中p16和MGMT基因启动子区甲基化的改变情况,评价该指标作为肺癌辅助诊断分子标志物的价值。方法：运用甲基化特异性PCR技术,检测77例原发性肺癌患者痰标本和部分对应肿瘤组织(53例),以及30例正常对照者痰标本中p16和MGMT基因启动子区域的甲基化改变。结果：49例(63．6%)肺癌患者痰标本中检测到了pi6基因异常甲基化,34例(44．2%)检测到了MGMT基因异常甲基化,77例患者痰标本中2个基因中至少有1个基因出现甲基化为64例(83．1%),对肿瘤的检出灵敏度较高。长期吸烟史是影响肺鳞状细胞癌痰标本p16(P=0．001)基因启动子区甲基化的因素。随TNM分期增高,肺鳞状细胞癌患者痰标本中p16基因甲基化比例增高(P=0．021)；随TNM分期增高,肺腺癌患者痰标本MGMT基因甲基化比例增高(P=0．023)。对照组正常人痰液标本未发现p16和MGMT基因启动子区甲基化。结论：痰标本中p16和MGMT基因甲基化是临床肺癌辅助诊断的有效生物标志物之一。

Diagnostic value of hypermethylation of p16 and MGMT genes in sputum specimens for lung cancer

Objective:To analyze the aberrant methylation of p16 and MGMTpromoter in sputum specimens from lung canc- er patients and to estimate the value of p16 and MGMT hypermethylation as an effective marker for the early auxiliary diagnosis of lung cancer.Methods:Sputum specimens and the corresponding partial tumor tissue samples were collected from 77 lung canc- er patients and 30 normal healthy controls.Methylation-specifie PCR (MSP) was performed for the detection of aberrant methyl- ation of p16 and MGMT in promoter regions.Results:The hypermethylation of p16 and MGMT in promoter regions were detec- ted in 49(63.6%)and 34 (44.2%) sputum specimens from lung cancer patients,respectively.Aberrant methylation of p16 and/ or MGMT was detected in sputum specimens from 64 (83.1%) lung cancer patients indicating that hypermethytation of p16 and MGMT in sputum samples could be a more sensitive and specific marker for the diagnosis of lung cancer.Compared with non- smokers patients with long smoking history(patients with adenoearcinoma) had significantly higher risk of hypermethylation of p16 (P=0.001) in promoter regions.The frequency of p16 hypermethylation increased significantly with the advance of TNM staging in squamous cell carcinoma (P=0.021).The frequency of MGMT hypermethylation increased significantly with the ad- vance of TNM staging in adenocarcinoma (P=0.023).In 30 cases of normal controls,hypermethylation of p16 and MGMT was not detected.Conclusion:Hypermethylation of p16 and MGMT genes in sputum specimens was one of the effective biological markers for the earlier auxiliary diagnosis of lung cancer.