老年肺癌病人痰标本中p16基因异常甲基化的研究

Analysis of p16 hypermethylation in sputum samples from elderly patients with lung cancer

目的分析老年肺癌病人痰标本中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聚合酶链反应技术,检测94例老年原发性肺癌病人痰标本和部分对应肿瘤组织,以及10例慢性肺炎病例痰标本中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(46.8%)相比,痰标本中p16基因异常高甲基化对肿瘤的检出率(74.5%)灵敏度更高(P<0.01);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例慢性肺炎病人痰标本中仅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 aberrantmethylation of p16 promoter in sputum samples from elderly patients with lung cancer and to evaluate pl6 hypermethylation as an effective biomarker for the early auxilliary diagnosis of lung cancer. Methods 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 and 10 cases of chronic lung inflammation. Results The hypermethylation of p16 promoter was detected in 74% of the sputum specimens. Com- pared 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 pl6 hypermethylation in sputum could identify 86. 17% （81/94） of lung cancer. The patients whose sputum cells had hypermethylated p16 gene also exhibited aberrant methylation in their tumor cells. In 10 cases of chronic lung inflammation, p16 hypermethylation was only detected in 3 cases. Conclusions Detection of p16 hypermethylation in sputum of the patients with lung cancer might offer an effective method for the earlier auxiliary diagnosis of lung cancer.