NDRG2基因在贲门腺癌中的甲基化状态及表达

目的： 探讨贲门腺癌(GCA)中NDRG2(N-myc downstream-regulated gene 2)基因启动子区的甲基化状态，并分析其甲基化与表达之间的相关性。方法：应用甲基化特异性PCR(MSP)方法检测97例贲门腺癌组织及相应癌旁组织中NDRG2基因的甲基化状态，应用RT-PCR和免疫组织化学方法检测97例贲门腺癌组织及相应癌旁组织中NDRG2的mRNA和蛋白表达情况。结果：NDRG2基因启动子区在贲门腺癌组织中的甲基化率(49.5%)显著高于癌旁正常组织(5.1%)(P<0.05)，且Ⅲ期和Ⅳ期贲门腺癌患者中NDRG2基因甲基化的比率显著高于Ⅰ期和Ⅱ期患者，低分化组中NDRG2基因发生甲基化的比率显著高于高中分化组。贲门腺癌组织中NDRG2 mRNA表达水平显著低于癌旁正常组织(P<0.05)。贲门腺癌组织中NDRG2蛋白表达阳性率为44.3%(43/97)，显著低于相应癌旁正常组织的蛋白表达94.8%(92/97)(P<0.01)，且贲门腺癌组织中NDRG2蛋白表达缺失与其启动子区的甲基化有明显的相关性(r=-0.510，P<0.01)。结论：NDRG2基因启动子区的高甲基化导致的基因沉默可能是贲门腺癌中此基因表达降低的机制之一。

Promoter methylation status and expression of NDRG2 gene in gastric cardia adenocarcinoma

OBJECTIVE: To investigate the promoter methylation status of N-myc downstream-regulated gene 2 (NDRG2) and its correlation with mRNA and protein expressions of the gene in gastric cardia adenocarcinoma (GCA). METHODS：MSP method was used to measured the promoter methylation status of NDRG2 in 97 GCA tumor tissues and corresponding normal tissues. RT-PCR and immunohistochemistry were used to examine mRNA and protein expression，respectively，of NDRG2 in 97 GCA tumor tissues and corresponding normal tissues. RESULTS：The promoter methylation frequency of NDRG2 in GCA tumor tissues (49.5%) was significantly increased in comparison to that in corresponding normal tissues (5.1%) (P<0.05). The methylation frequency of NDRG2 in stages Ⅲ and Ⅳ tumor tissues was significantly higher than that in stages Ⅰ and Ⅱ tumor tissues. The methylation frequency of NDRG2 in poorly differentiated group was significantly higher than that in well and moderately differentiated group (P<0.05). NDRG2 mRNA expression in tumor tissues was significantly lower than that in corresponding normal tissues (P<0.05). Positive protein expression of NDRG2 in tumor tissues (44.3%，43/97) was significantly lower than that in corresponding normal tissues (94.8%，92/97) (P<0.01). The protein expression of NDRG2 was inversely correlated with its promoter methylation status in GCA tissues. CONCLUSION：Promoter hypermethylation of NDRG2 may be one of the mechanisms that lead to gene inactivation in gastric cardia adenocarcinoma.