肺癌组织p16基因启动子区高甲基化情况分析

目的:了解不同临床病理情况下肺癌组织中p16基因启动子区高甲基化的情况。方法:采用甲基化特异的PCR(MSP)法,根据5-甲基胞嘧啶与胞嘧啶修饰后的不同,设计甲基化与非甲基化等位基因特异的引物,通过PCR扩增检测手术后53例不同临床病理类型肺癌组织中p16基因启动子区高甲基化情况。结果:肿瘤组织标本中p16基因启动子区甲基化比例为占71.7%(38/53),其中鳞状细胞癌占80.0%(20/25),腺癌占66.7%(10/15),小细胞肺癌占61.5%(8/13)。长期吸烟史与鳞状细胞癌p16基因启动子区高甲基化比例增高有关(P<0.001),与小细胞肺癌(P=0.293)、腺癌的(P=1.000)p16基因启动子区高甲基化关系不密切。肿瘤T分期与鳞状细胞癌p16基因启动子区高甲基化比例增高有关(χ2=8.719,P=0.013)。结论:肺癌瘤组织标本中p16基因启动子区高甲基化是比较常见的现象;肿瘤组织基因启动子区高甲基化发生率随TNM分期的提高有升高趋势;基因启动子区甲基化状态与吸烟有关,有长期吸烟史的肺癌病人p16基因启动子区甲基化率增高。肺鳞状细胞癌中随T分期增高p16基因启动子区高甲基化比例增高。

Aberrant methylation of the p16 gene promoter region in lung cancer

Objective:To study the aberrant methylation of the p16 gene promoter regions in lung cancer. Methods:Promoter hypermethylation status of the p16 gene was evaluated in tumor tissue from 53 patients with lung cancer using methylation-specific-PCR (MSP). Results:The results showed hypermethylated p16 sequence in 71.7%(38/53) of tumor tissues, including 80.0%(20/25) of squamous cell carcinoma,66.7%(10/15) of adenocarcinoma, and 61.5%(8/13) of small cell lung cancer, respectively. More tumors from smokers exhibited p16 methylation than non-smokers did (73.2% versus 38.1%). The frequency of p16 methylation increased significantly with the progress of tumor T-stage in squamous cell carcinoma(χ~2=8.719, P=0.013). Conclusion: This study demonstrates that p16 promoter hypermethylation is a common event in lung cancer. The frequency of p16 methylation increases significantly with the progress of tumor stage. High frequency of p16 methylation can be seen in smokers compared with non-smokers.