肺癌病人痰细胞中p16基因高甲基化分析

Analysis of p16 hypermethylation in sputum samples from lung cancer patients

目的 分析肺癌病人痰标本中p16基因启动子区域异常高甲基化的改变情况 ,评价该指标作为肺癌辅助诊断分子标记物的价值。方法 运用半巢式甲基化特异性PCR技术 ,检测 94例原发性肺癌病人痰标本和部分对应肿瘤组织 ,以及 10例慢性炎病例痰标本中p16基因启动子区域的甲基化改变。结果 74%的肺癌病人痰标本中检测到了p16基因异常高甲基化 ,与传统细胞学相比 ( 4 6.8%) ,痰标本中p16基因异常高甲基化对肿瘤的检出率灵敏度更高 (P <0 .0 1) ;痰细胞中p16甲基化检测和细胞学相结合 ,对肿瘤的检出率可达 86.17%( 81 94)。如果痰标本中p16基因启动子区域发生高甲基化 ,其对应的肿瘤组织中p16基因亦为高甲基化。 10例慢性炎病人痰标本中仅 3例检测出p16基因甲基化。结论 痰标本中p16基因甲基化是临床肺癌辅助诊断的有效分子生物标记物之一。

Objective To analyze the aberrant methylation of p16 promoter in sputum samples from lung cancer patients and to evaluate p16 hypermethylation as an effective biomarker for the early auxilliary diagnosis of lung cancer. Methods A modified semi nested methylation specific PCR (MSP) was performed for the detection of p16 hypermethylation in sputum and corresponding partial tumor tissue samples from 94 cases of lung cancer patients and 10 cases of chronic inflammation. Results The hypermethylation of p16 promoter was detected in 74% of the sputum specimens. Compared with conventional cytological analysis, detection of p16 hypermethylation in sputum samples could be a more sensitive and specific approach for the diagnosis of lung cancer. Combination of cytological analysis and detection of p16 hypermethylation in sputum could identify 86.17% (81/94) lung cancer. The patients whose sputum cells had hypermethylated p16 gene also exhibited aberrant methylation in their tumor cells. In 10 cases of chronic inflammation, p16 hypermethylation was only detected in 3 cases. Conclusion Detection of p16 hypermethylation in sputum of the lung cancer patients might offer an effective means for the earlier auxillary diagnosis of this malignancy.