目的:探讨非小细胞肺癌(NSCLC)中ASC基因启动子甲基化与患者临床特征之间的关系以及去甲基化试剂对肺癌细胞系中ASC基因甲基化状态的逆转。方法:应用甲基化特异性PCR(MSP)检测48例NSCLC患者肿瘤组织和3株肺癌细胞系中ASC基因的甲基化状态,RT—PCR检测去甲基化试剂诱导肺癌细胞系中甲基化ASC基因的重新表达。结果:NSCLC肿瘤组织和相对应的正常肺组中ASC基因启动子甲基化的发生率分别为49.7%和8-3%,二者之间有显著性差异(P〈0.01)。重度吸烟患者的肿瘤组织中ASC基因启动子甲基化的发生率明显增高(P〈0.05),早期的NSCLC(T1)中ASC基因启动子甲基化也有相对较高的发生率(P〈0.05)。去甲基化试剂5-氮-2’-脱氧胞苷(5-aza-2'-deoxycytidine)可使甲基化的ASC基因启动子发生逆转而获得重新表达。结论:ASC基因启动子的甲基化可能与吸烟引起的非小细胞肺癌有关.并可能是非小细胞肺癌发展过程中的一个早期事件,甲基化的ASC基因可以成为NSCLC治疗的靶点。
objective: To investigate the correlation between methylation of the ASC gene promoter region and the clinical characteristics of patients with non-small cell lung cancers and to determine whether the methylation of the ASC gene can be reversed by a demethylation agent. Methods: Methylation-specific PCR (MSP) was performed to detect methylation of the ASC gene promoter in 48 patients with NSCLC and in 3 lung cancer cell lines, and RT-PCR was employed to examine the restoration of expression in lung cancer cell lines after treating with the demethylation agent 5-aza-2'-deoxycytidine. Results:The frequency of ASC gene methylation in cancer tissues was significantly different from that in adjacent normal tissues (47.9% to 8.3%, P〈0.001). There was a higher rate of ASC gene methylation in the tumor tissues of heavy smokers (P〈0.05) and in early stage NSCLC(T1) (P〈0.05). Expression of the methylated ASC gene was restored after cells were treated with the demethylation agent. Conclusions: Methylation of the ASC gene promoter may be related to NSCLC caused by smoking and may be an early event in the genesis of NSCLC. Methylated ASC gene promoters may be a target in the treatment of NSCLC.