摘要
目的:探讨贲门腺癌(gastric cardiac adenocarcinoma,GCA)中凋亡蛋白酶活化因子-1(apoptosis protease activatingfactor-1,Apaf-1)基因启动子区甲基化状态及其与果蝇zeste基因增强子人类同源物2(enhancer of zeste homolog 2,EZH2)蛋白表达之间的相关性。方法:应用甲基化特异性PCR(methylation specific polymerase chain reaction,MSP)检测GCA组织及癌旁组织中Apaf-1基因甲基化状态,应用免疫组织化学法检测GCA组织及癌旁组织中Apaf-1和EZH2蛋白的表达情况。结果:GCA组织中Apaf-1基因甲基化率显著高于癌旁组织[49.6%(62/125)vs 4.0%(5/125),P<0.01],Ⅲ期和Ⅳ期GCA组织中Apaf-1基因甲基化率显著高于Ⅰ期和Ⅱ期(58.8%vs 38.6%,P<0.05),但GCA组织中Apaf-1基因甲基化率与GCA的组织学分化程度无关(P>0.05)。GCA组织中Apaf-1蛋白表达阳性率显著低于相应癌旁组织(39.2%vs 96.0%,P<0.01),且与Apaf-1基因甲基化状态相关。GCA组织中EZH2蛋白表达阳性率显著高于相应癌旁组织(74.4%vs 11.2%,P<0.01),且与Apaf-1蛋白的表达呈负相关。结论:GCA组织中Apaf-1基因启动子区呈高甲基化,Apaf-1和EZH2蛋白可能共同参与了GCA的发展。
Objective ： To investigate the methylation of apoptosis protease activating factor-1 （ Apaf-1） gene promoter and its correlation with protein expression of enhancer of zeste homolog 2 （EZH2） in gastric cardia adenocarcinoma （GCA）. Methods： Methylation specific polymerase chain reaction （MSP） method was used to examine the methylation status of Apaf-1 gene, and immunohistochemistry method was used to detect the protein expression of Apaf-1 and EZH2 in GCA and paracancerous tissues. Results： The frequency of Apaf-1 methylation in GCA tissues （49.6%, 62/125） was significantly higher than that in paracancerous tissues （4.0%, 5/125, P〈0.01）. The methylation frequencies of Apaf-1gene in stage Ⅲ and Ⅳ GCA tissues were significantly higher than those in stage Ⅰ and Ⅱ GCA tissues （58.8% vs 38.6%, P〈0.05）. No significant difference in the methylation frequency of Apaf-1 gene was found in three histological differentiated groups （P〉0.05）. The positive protein expression of Apaf-1 in GCA tissues was significantly decreased compared with paracancerous tissues （39.2% vs 96.0%, P〈0.01） and was correlated with its methylation status. The positive protein expression of EZH2 in GCA tissues was significantly increased compared with that in paracancerous tissues （744% vs 11.2%, P〈0.01） and was negatively correlated with the expression of Apaf-1 protein in GCA. Conclusion： The promoter of Apaf-1 gene is hypermethylated and both Apaf-1 and EZH2 may play important roles in the development of GCA.
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
北大核心
2012年第5期526-530,共5页
Chinese Journal of Cancer Biotherapy
基金
河北省医学科学研究重点课题资助(No.20090465)~~
关键词
贲门腺癌
凋亡蛋白酶活化因子-1基因(Apaf-1)
DNA甲基化
EZH2蛋白
gastric cardia adenocarcinoma apoptosis protease activating factor-1（ Apaf-1） DNA methylation enhancer of zeste homolog 2 protein （EZH2）
