子宫内膜癌中DKK-1基因启动子低甲基化改变与其临床病理特征的关系

The Correlation of Promoter Hypomethylation of DKK-1 Gene in Endometrial Carcinoma and Its Clinicopathological Characteristics

目的探索Dickkopf相关蛋白1(DKK-1)基因启动子区甲基化变化与子宫内膜癌临床病理特征的关系。方法采用甲基化特异性PCR(methylation-specific PCR,MSP)对52例子宫内膜癌、30例子宫内膜不典型增生患者及25例正常子宫内膜受试者进行DNA甲基化状态检测。免疫组织化学[链霉菌抗生物素蛋白-过氧化物酶连结(immunohistochemistry,streptomyces antibiotin protein-peroxidase binding,IHC S-P)]法测定雌激素受体、孕激素受体在子宫内膜癌细胞中的表达。结果检测到38例(73.08%)子宫内膜癌组织中DKK-1基因启动子区发生低甲基化改变,而子宫内膜非典型增生组织中为14例(46.67%)及正常子宫内膜组织为9例(36.00%)(χ^(2)=11.289,P=0.030)。DKK-1低甲基化阳性率在子宫内膜癌患者的不同国际妇产科联盟(FIGO)分期、病理类型和分级、雌、孕激素受体表达中差异具有统计学意义(P=0.043)。结论DKK-1基因启动子区低甲基化可能是子宫内膜癌发生中的早期且频发事件,且可能与子宫内膜癌的侵袭、迁移和不良预后密切相关。

Objective To investigate the relationship between methylation of promoter region of Dickkopf-associated protein 1(DKK-1)gene and endometrial carcinoma.Methods Methylation-specific polymerase chain reaction(MSP)was applied to detect the methylation status of DKK-1 gene in 52 samples of endometrial cancer,including 30 samples of endometrium and 25 samples of normal endometrium.The relationship between the methylation status of DKK-1 gene and different clinicopathological features of endometrial carcinoma was evaluated.The expressions of estrogen and progesterone receptors in endometrial carcinoma were detected by immunohistochemical method of streptomyces antibiotin protein-peroxidase binding(IHC S-P).Results The DKK-1 promoter region was found in 38(73.08%)endometrial cancer tissues,14(46.67%)normal endometrium and 9(36.00%)normal endometrium(χ^(2)=11.289,P<0.05).There were significant differences in the positive rate of DKK-1 hypomethylation among different FIGO stages,pathological types,histological grades,expressions of estrogen and progesterone receptors of endometrial carcinoma patients(P<0.05).Conclusion DKK-1 promoter hypomethylation is not only an early and frequent event in the occurrence of endometrial carcinoma,but also could be involved in the development of invasion and migration of endometrial carcinoma and is associated with the poor prognosis.The hypomethylation of DKK-1 gene promoter can be one of the potential causes of the poor prognosis of female,progesterone receptor-negative endometrial carcinoma and non-endometrial carcinoma.