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 activating factor-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STBX 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-1gene 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 (744% 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.

河北省医学科学研究重点课题资助（No. 20090465）