Liu Yong, An Qian, Li Ling, Zhang Dechao, Huang Jinfeng, Feng Xiaoli, Cheng Shujun, Gao Yanning
Department of Chemical Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, P.R.China.
Carcinogenesis. 2003 Dec;24(12):1897-901. doi: 10.1093/carcin/bgg169. Epub 2003 Sep 11.
Promoter hypermethylation of the p16INK4a gene was investigated in 111 cases of tumor tissue, as well as in 136 circulating plasma and 95 sputum samples from Chinese patients with primary lung cancer, using a modified protocol of semi-nested methylation-specific-PCR (MSP). The results showed hypermethylated p16 sequence in 80.2% of tumor tissues and frequencies of 75.7 and 74.7% in plasma and sputum specimens, respectively. Among the patients, 50 cases of matched plasma, sputum and tumor tissue from the same individual were analyzed. Of these, hypermethylation of the p16 promoter was detected in 84.0% of the tumor tissues, with frequencies of 72.0 and 76.0% in the corresponding plasma and sputum, respectively. Notably, only patients whose tumor tissue showed hypermethylation of p16 exhibited the same aberrant methylation in their sputum and/or plasma. Hypermethylation of p16 in sputum and plasma samples may provide a more sensitive approach to molecular diagnosis of lung cancer than relying on conventional cytological analysis. Our data show that a combination of cytological analysis of sputum and examination of p16 hypermethylation in sputum and plasma identified 92.0% (46/50) of the lung cancer patients studied, offering an effective means of early detection of lung cancer.
采用改良的半巢式甲基化特异性聚合酶链反应（MSP）方案，对111例肿瘤组织以及136份中国原发性肺癌患者的循环血浆样本和95份痰液样本进行p16INK4a基因启动子高甲基化研究。结果显示，80.2%的肿瘤组织中存在p16序列高甲基化，血浆和痰液样本中的频率分别为75.7%和74.7%。在这些患者中，对来自同一患者的50例配对血浆、痰液和肿瘤组织进行了分析。其中，84.0%的肿瘤组织检测到p16启动子高甲基化，相应血浆和痰液中的频率分别为72.0%和76.0%。值得注意的是，只有肿瘤组织显示p16高甲基化的患者，其痰液和/或血浆中才出现相同的异常甲基化。与依靠传统细胞学分析相比，痰液和血浆样本中p16高甲基化可能为肺癌分子诊断提供更敏感的方法。我们的数据表明，痰液细胞学分析与痰液和血浆中p16高甲基化检测相结合，可识别92.0%（46/50）的研究肺癌患者，为肺癌早期检测提供了一种有效手段。
