痰标本p16和MGMT基因甲基化对肺癌的诊断价值

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

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。

Objective：To analyze the aberrant methylation of p16 and MGMT promoter in sputum specimens from lung cancer 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 cancer patients and 30 normal healthy controls. Methylation-specific PCR （MSP） was performed for the detection of aberrant methylation of p16 and MGMT in promoter regions. Results： The hypermethylation of p16 and MGMT in promoter regions were detected 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 hypermethylation of p16 and MGMT in sputum samples could he a more sensitive and specific marker for the diagnosis of lung cancer. Compared with nonsmokers patients with long smoking history（patients with adenocarcinoma） 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 advance 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.