上皮性卵巢癌患者血清无细胞DNA MEG3甲基化状态及临床意义

The methylation status of serum cell-free DNA MEG3 in epithelial ovarian cancer and its clinical significance

目的 通过检测上皮性卵巢癌患者血清无细胞DNA中MEG3基因的甲基化状态,分析MEG3基因的甲基化状态在上皮性卵巢癌诊断中的临床意义。方法 通过甲基化特异性PCR(MSP)检测60例上皮性卵巢癌(实验组)和30例非肿瘤患者(对照组)血液标本中血清无细胞DNA MEG3基因启动子甲基化状态,分析浆液性癌、黏液性癌、子宫内膜样癌和透明细胞癌4种不同病理类型上皮性卵巢癌的无细胞DNA MEG3基因启动子甲基化率;分析不同临床分期、不同分化程度、有无淋巴结转移的上皮性卵巢癌的无细胞DNA MEG3基因启动子甲基化率的差异。对60例上皮性卵巢癌病例甲基化状态分两组进行生存分析。结果 上皮性卵巢癌组MEG3基因启动子甲基化率为80%,而对照组甲基化率为13.3%;>60岁与≤60岁两组间甲基化率比较,差异均无统计学意义(均P>0.05);浆液性癌、黏液性癌、子宫内膜样癌和透明细胞癌4种不同病理类型的甲基化率分别是84.0%、91.7%、53.8%、81.8%,差异无统计学意义(P>0.05)。临床分期Ⅰ~Ⅱ期的MEG3基因启动子甲基化率为30.8%,Ⅲ~Ⅳ期的甲基化率为91.5%;中高分化的MEG3基因启动子甲基化率为72.0%,低分化MEG3基因启动子甲基化率为82.9%;有淋巴结转移组的MEG3基因启动子甲基化率为90.5%,无淋巴结转移组的甲基化率为50.0%。生存分析显示甲基化组(M组)的5年生存率为19.6%,非甲基化组(U组)的5年生存率为59.8%;M组的中位生存期为33个月。结论 血清无细胞DNA MEG3基因启动子甲基化有望成为诊断上皮性卵巢癌的潜在标志物。

Objective To detect the methylation status of MEG3 gene in serum cell-free DNA of patients with epithelial ovarian cancer and analyze the clinical significance of the methylation status of MEG3 gene in the diagnosis of epithelial ovarian cancer.Methods Methylation-specific PCR(MSP) was used to detect the methylation status of serum cell-free DNA MEG3 gene promoter in blood samples of 60 cases of epithelial ovarian cancer(experimental group) and 30 cases of non-tumor patients(control group). Analyze the cell-free DNA MEG3 gene promoter methylation rate of four different pathological types of epithelial ovarian cancer of serous carcinoma, mucinous carcinoma, endometrioid carcinoma and clear cell carcinoma;analyze different clinical stages, different degrees of differentiation, and The difference in the methylation rate of the cell-free DNA MEG3 gene promoter in epithelial ovarian cancer without lymph node metastasis. The methylation status of 60 cases of epithelial ovarian cancer were divided into two groups for survival analysis.Results The methylation rate of the MEG3 gene promoter in the epithelial ovarian cancer group was 80%, while the methylation rate of the control group was 13.3%. There was no statistically significant difference in the methylation rate between the two groups over 60 years old and less than or equal to 60 years old.(P>0.05);The methylation rates of four different pathological types of serous carcinoma, mucinous carcinoma, endometrioid carcinoma and clear cell carcinoma are 84.0%, 91.7%, 53.8%, and 81.8%, respectively, and there is no statistical difference Academic significance(P>0.05). The methylation rate of the MEG3 gene promoter in clinical stages Ⅰ-Ⅱ is 30.8%, the methylation rate of the Ⅲ-Ⅳ stage is 91.5%;the methylation rate of the MEG3 gene promoter is 72.0% in the middle and high-differentiation, and the methylation rate in the poorly-differentiated MEG3 The methylation rate of gene promoter was 82.9%;the methylation rate of MEG3 gene promoter in the group with lymph node metastasis was 90.5%, and the methylation rate in the group without lymph node metastasis was 50.0%. Survival analysis showed that the 5-year survival rate of the methylated group(M group) was 19.6%, the 5-year survival rate of the unmethylated group(U group) was 59.8%;the median survival of the M group is 33 months.Conclusion Serum cell-free DNA MEG3 gene promoter methylation is expected to be a potential marker for the diagnosis of epithelial ovarian cancer.