Dickkopf-1基因在宫颈鳞癌组织中的甲基化研究

目的检测Dickkopf-1(DKK1)基因在宫颈鳞癌组织中的甲基化状态,分析其临床意义。方法采用甲基化特异性聚合酶链反应(MSP)检测28例宫颈炎、20例CINⅠ、31例CINⅡ~Ⅲ及36例宫颈鳞癌组织中DKK1基因启动子区甲基化情况,并分析宫颈鳞癌组织中DKK1基因甲基化水平与临床病理特征之间的相关性。结果宫颈炎、CINⅠ、CINⅡ~Ⅲ和宫颈鳞癌组中DKK1基因甲基化阳性率分别为10.7%、10%、32.3%和44.4%。宫颈鳞癌组织的甲基化阳性率明显高于宫颈炎和CINⅠ组,DKK1基因启动子甲基化与肿瘤分化程度以及肿瘤的直径相关。结论 DKK1基因启动子区甲基化检测可能为宫颈鳞癌的诊断以及鉴别诊断提供一个新的检查方法。

Analysis of Dickkopf-1 promoter methylation status in human primary cervical squamous cell carcinoma

Objective To detect the promoter methylation status of Dickkopf-1(DKK1) gene in human cervical squamous cell carcinoma tissues and evaluate its correlation with clinicopathological features.Methods Tissue specimens were obtained from a total of 115 patients undergoing curative surgery,hysterectomy,loop electrosurgical excision procedure or colposcopy and biopsy,including 28 patients diagnosed of cervicitis,20 patients with cervical intraepithelial neoplasias(CIN) Ⅰ,31 patients with CIN Ⅱ-Ⅲ and 36 patients diagnosed of cervical squamous cell carcinoma.Promoter methylation status of DKK1 gene was determined by methylation-specific polymerase chain reaction(MSP),and the correlation between methylation profiles and clinicopathological parameters was statistically analyzed.Results Aberrant methylation of DKK1 gene was detected in 3 of 28(10.7%) cervicitis,2 of 20(10%) CIN Ⅰ tissues,10 of 31(32.3%) CIN Ⅱ-Ⅲ and 16 of 36(44.4%) cervical squamous cell carcinoma tissues.The methylation status of the malignant group was significantly higher than that in the benign group and CIN Ⅰ group.Moreover,DKK1 hypermethylation was correlated with tumor differentiation and the diameter of tumor.Conclusion Detection of DKK1 methylation in cervical tissues may provide a new method for the diagnosis and differential diagnosis of human squamous cell carcinoma.