Hypermethylation of p16INK4a in Chinese lung cancer patients:: biological and clinical implications
Hypermethylation of p16INK4a in Chinese lung cancer patients:: biological and clinical implications
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DOI：
10.1093/carcin/bgg169
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发表时间：
2003-12-01
期刊：
影响因子：
4.7
通讯作者：
Gao, YN
中科院分区：
文献类型：
--
作者：
Liu, Y;An, Q;Gao, YN
应用改良的半巢式甲基化特异性PCR（MSP）方法检测了111例肺癌组织、136例循环血浆和95例痰标本中p16（INK 4a）基因启动子区的甲基化。结果显示，80.2%的肿瘤组织中存在p16基因的高甲基化，血浆和痰标本中的高甲基化率分别为75.7%和74.7%。在患者中，分析了50例来自同一个体的匹配的血浆、痰和肿瘤组织。其中，p16基因启动子甲基化在84.0%的肿瘤组织中检测到，在相应的血浆和痰中的频率分别为72.0%和76.0%。值得注意的是，只有肿瘤组织显示p16高甲基化的患者在其痰液和/或血浆中显示相同的异常甲基化。痰液和血浆中p16的高甲基化可能为肺癌的分子诊断提供比依赖于常规细胞学分析更敏感的方法。我们的数据显示，痰细胞学分析和痰及血浆中p16高甲基化检测相结合的肺癌患者的识别率为92.0%（46/50），提供了一个有效的手段，肺癌的早期发现。
Promoter hypermethylation of the p16(INK4a) 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.