肺癌患者外周血血浆中p16基因异常甲基化的检测  

Detection of hypermethylation of p16 gene in plasma DNA from lung cancer patients

作　　者：刘晋祎[1] 安倩[1] 许冠东[1] 雷文东[2] 冯晓莉[3] 郭素萍[1] 程书钧[1] 高燕宁[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院病因及癌变研究室 [2]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院胸外科,北京100021 [3]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院病理科,北京100021

出　　处：《中华肿瘤杂志》2004年第3期154-157,共4页Chinese Journal of Oncology

基　　金：国家重点基础研究发展规划项目 (G19980 5 12 0 7) ;国家科技攻关计划项目 (2 0 0 2BA711A0 6)

摘　　要：目的　分析肺癌患者外周血血浆中p16基因启动子区异常甲基化发生情况 ,探讨血浆中p16基因异常改变作为肺癌临床辅助诊断分子生物学标志物的可能性。方法　利用半巢式甲基化特异性PCR技术 ,检测了 137例肺癌患者血浆和 112例相对应肿瘤组织DNAp16基因的异常甲基化情况。结果　在血浆和肿瘤组织中的p16基因甲基化检出率分别为 75 .2 %和 80 .4 % ;其中鳞癌、腺癌、腺鳞癌和小细胞肺癌患者血浆标本的阳性率分别为 77.9% ,6 5 .1% ,75 .1%和 91.7%。血浆DNAp16基因甲基化仅在肿瘤组织存在同样甲基化的病例中被检出。血浆和肿瘤组织中 ,p16基因的甲基化异常改变与肿瘤的分期、分型无明显相关性。结论　分析血浆DNA的p16基因异常甲基化有可能成为辅助肺癌诊断的有效方法之一。ObjectiveTo detect hyper methylation of p16 gene in plasma DNA from patients with lung cancer, and to assess its potential as a malignant marker. MethodsUsing a modified semi-nested methylation-specific PCR (MSP), the status of methylation of the p16 was investigated in plasma DNA from 137 lung cancer patients and 112 matched tumor tissues. ResultsHypermethylation of the p16 was present in 75.2%(103/137) of the plasma samples and 80.4% (90/112) of the tumor tissues. Hypermethylation of the p16 in the plasma was detected in 77.9% squamous-cell carcinoma, 65.1% adenocarcionma, 75.1% adeno-squamous-cell carcinoma, and 91.7% small-cell lung cancer. Only in those patients whose tumor tissues had hypermethylation of p16 gene, similar changes could be detected in their plasma samples. Hypermethylation of the p16 in plasma and the corresponding tumor tissues was not significantly correlated with the clinical stage and pathological type of the tumor. ConclusionThe result indicates that hypermethylation of the p16 may be a useful marker in the auxiliary diagnosis of lung cancer.

关 键 词：肺癌 外周血 P16基因 DNA甲基化 肿瘤标志物 PCR技术 辅助诊断 

分 类 号：R734.2[医药卫生—肿瘤]