子宫内膜癌患者肿瘤组织和血清中SOX1和VIM启动子的甲基化检测及其临床意义

Detection of methylation of SOX1 and VIM promoters in tumor tissues and serum from patients with endometrial carcinoma and its clinical significance

目的检测子宫内膜癌(EC)患者血清中性别决定区Y框蛋白1(SOX1)和波形蛋白(VIM)启动子的甲基化情况,并探究其临床意义。方法选择英山县人民医院2013年7月至2015年12月收治的120例EC患者为观察组,另选择50例功能性子宫出血患者作为对照组。采用甲基化特异性PCR(MSP)技术检测血清及肿瘤组织SOX1、VIM基因启动子的甲基化状态;分析血清SOX1、VIM基因启动子甲基化与EC患者临床病理特征的关系;并分析SOX1、VIM单一及联合检测方法的灵敏度、特异度和准确度。结果 (1)EC患者血清SOX1基因启动子甲基化率(71.67%)显著高于对照组(10.00%)(P<0.05),EC患者肿瘤组织SOX1基因启动子甲基化率(95.83%)显著高于对照组(2.00%)(P<0.05)。(2)EC患者血清VIM基因启动子甲基化率(60.83%)显著高于对照组(12.00%)(P<0.05),EC患者肿瘤组织VIM基因启动子甲基化率(94.17%)显著高于对照组(4.00%)(P<0.05)。(3)血清SOX1、VIM基因启动子甲基化水平与EC患者的淋巴结转移情况、病理分期、子宫肌层浸润深度有关(P<0.05),与HCC患者的年龄、肿瘤类型无关(P>0.05)。(4)血清SOX1、VIM启动子甲基化单独及联合诊断的灵敏度依次为71.67%、60.83%和81.67%,特异度依次为90.00%、88.00%和84.00%,准确度依次为77.06%、68.82%和86.47%。与SOX1、VIM单独诊断比较,联合诊断的灵敏度,准确度均显著升高(P<0.05);不同诊断方式的特异度比较差异无统计学意义(P>0.05)。结论 SOX1和VIM基因甲基化是EC发生的潜在标志物,血清SOX1和VIM基因启动子甲基化联合检测可用于临床EC的筛查及早期诊断。

Objective To detect the methylation status of sex-determining region Y-box protein 1(SOX1)and vimentin(VIM)promoters in serum from patients with endometrial carcinoma(EC),and to explore its clinical significance.Methods A total of 120 patients with EC who were admitted to Yingshan County People's Hospital from July 2013 to December 2015 were enrolled in the observation group,while 50 patients with functional uterine bleeding were recruited as the control group.Methylation-specific PCR(MSP)was used to detect the methylation status of the promoters of SOX1 and VIM gene in serum and tumor tissues.The relationship between the promoters of SOX1 and VIM methylation and clinicopathological features of EC patients was analyzed.The sensitivity,specificity and accuracy of SOX1 and VIM alone or combined detection were also analyzed.Results①The methylation rates of the promoter of SOX1 gene in serum and tumor tissues from EC patients(71.61%and 95.83%)were significantly higher than that in the control group(10.00%and 2.00%)(P<0.05).②The methylation rates of the promoter of VIM gene in serum and tumor tissues from EC patients(60.83%and 94.17%)were significantly higher than that in the control group(12.00%and 4.00%),(P<0.05).③The promotor methylation levels of SOX1 and VIM gene were correlated with the pathological staging,myometrial invasion depth and lymph node metastasis in patients with EC patients(P<0.05),and not associated with the patient’s age or tumor type of HCC(P>0.05).④The sensitivity of serum of the promoter of SOX1 and VIM methylation alone and combined diagnosis was 71.67%,60.83%,81.67%,and the specificity was 90.00%,88.00%,84.00%,and the accuracy was 77.06%,68.82%,86.47%,respectively.Compared with SOX1 and VIM alone,the sensitivity and accuracy of combined diagnosis significantly increased(P<0.05).There was no significant difference in the specificity of different diagnostic methods(P>0.05).Conclusion The methylation of the SOX1 and VIM genes are potential markers for EC.The combined detection of the SOX1 and VIM gene methylation in promoters can be used for clinical EC screening and early diagnosis.