非小细胞肺癌组织中Apaf-1基因表达及启动子区甲基化研究

目的:探讨Apaf1基因表达及启动子区甲基化在非小细胞肺癌(nonsmallcelllungcancer,NSCLC)发生中的作用。方法:应用免疫组化、半定量RTPCR和甲基化特异性PCR方法分析45例NSCLC及癌旁正常对照组织中Apaf1(apoptoticproteaseactivatingfactor1)基因的表达及启动子区甲基化情况。结果:60%(27/45)NSCLC组织Apaf1表达明显下调,与癌旁正常组织相比差异有统计学意义,P=0.0005。在Apaf1基因表达明显下调的27例NSCLC中19例出现甲基化,表达水平无明显变化的18例NSCLC中5例出现甲基化;二者对比差异有统计学意义,P=0.005。45例癌旁正常对照组织未检测到Apaf1基因启动子甲基化,提示启动子区甲基化是Apaf1基因表达下调的主要原因。结论:Apaf1基因与NSCLC相关,启动子区甲基化是该基因失活的重要机制。

Study on expression and promoter methylation of Apaf-1 gene in non-small cell lung cancer

OBJECTIVE:To investigate the effect of Apaf-1 in progression of NSCLC (non- small cell lung cancer,NSCLC). METHODS:The expression of Apaf-1 gene and methylation of Apaf-1(apoptotic protease activating factor-1) promoter were analyzed by immunohistochemical, RT-PCR and methylation specific PCR (MSP) in 45 NSCLC tumor tissues and normal lung tissues. RESULTS: Apaf-1 gene expression was obviously down-regulated in 60%(27/45) of NSCLC,P=0.000 5. Nineteen cases of Apaf-1 gene methylation were detected in 27 cases with obvious down-regulation expression of Apaf-1,but 5 cases methylation were found in 18 cases in which the expression of Apaf-1 gene had no obvious change. The difference of the two groups had statistical significance,P=0.005. No methylation was found in 45 normal lung tissues. CONCLISION:This study confirmed the association between Apaf-1 gene and NSCLC,and DNA methylation in promoter region participates in the decreased expression of Apaf-1 gene in NSCLC.