SFRP1、LINE1基因启动子区CpG岛甲基化状态在肝细胞癌预后评估的价值

发布时间：2018-04-29 13:39

本文选题：肝癌 + 血浆　；参考：《四川大学学报(医学版)》2016年06期

【摘要】：目的探讨分泌型卷曲相关蛋白(SFRP)1、长散在核元件(LINE)1基因启动子区CpG岛甲基化与人原发性肝癌(简称肝癌)临床病理参数的关系,及其在肝癌预后评估的意义。方法收集105例肝癌患者血浆和50例对照健康人血浆DNA,使用甲基化特异性PCR(MSP)检测了SFRP1基因启动子区CpG岛高甲基化和LINE1基因启动子区CpG岛低甲基化的情况;分析两种基因启动子甲基化和肝癌患者临床病理参数之间的关系;通过Kaplan-Meier曲线、对数秩检验及Cox多因素分析,分析SFRP1、LINE1基因甲基化状态与肝癌患者总生存率及无病生存率之间的关系。结果105例肝癌患者血浆中SFRP1基因启动子区CpG岛高甲基化阳性率为59.05%(62/105),LINE1基因启动子区CpG岛低甲基化率为66.67%(70/105),基因SFRP1高甲基化和LINE1低甲基化表达均阳性为43.81%(46/105),正常对照组中未发现有这两种基因甲基化;SFRP1高甲基化、LINE1低甲基化均与HBsAg是否阳性及甲胎蛋白(AFP)值相关(P0.05);SFRP1、LINE1基因启动子区域的甲基化状态与总生存率及无病生存率有关:SFRP1高甲基化阴性+LINE1低甲基化阴性组患者预后最好,而SFRP1高甲基化阳性+LINE1低甲基化阳性组患者预后最差。结论 SFRP1、LINE1基因启动子区CpG岛甲基化与肝癌的发生、发展有一定联系,SFRP1和LINE1基因甲基化状态可以作为潜在可靠的分子标记物对患者预后进行预测。
[Abstract]:Objective to investigate the relationship between CpG island methylation and clinicopathological parameters in the promoter region of secretory crimp associated protein (SFRP1) and its prognostic value in patients with hepatocellular carcinoma (HCC). Methods Plasma DNAs were collected from 105 patients with hepatocellular carcinoma and 50 healthy controls. The hypermethylation of CpG island in the promoter of SFRP1 gene and the hypomethylation of CpG island in the promoter of LINE1 gene were detected by methylation specific PCR- MSPs. The relationship between promoter methylation of two genes and clinicopathological parameters of patients with liver cancer was analyzed by Kaplan-Meier curve, logarithmic rank test and Cox multivariate analysis. To analyze the relationship between the methylation status of SFRP1 / LINE1 gene and the overall survival rate and disease-free survival rate in patients with liver cancer. Results the positive rate of hypermethylation of CpG island in promoter region of SFRP1 gene was 59.05 in 105 patients with liver cancer. The hypomethylation rate of CpG island in promoter region of SFRP1 gene was 66.6770 / 105, and the positive rate of SFRP1 hypermethylation and LINE1 hypomethylation was 43.8146r105in normal control group. It was not found that the hypermethylation of SFRP1 and hypomethylation of SFRP1 were correlated with the HBsAg positive and AFP value of SFRP1 gene promoter. The methylation status in the promoter region of SFRP1 gene was correlated with the overall survival rate and disease-free survival rate. The patients with negative LINE1 hypomethylation negative had the best prognosis. The patients with SFRP1 hypermethylation positive LINE1 hypomethylation positive had the worst prognosis. Conclusion the methylation of CpG island in the promoter region of SFRP1 / LinE1 gene is associated with the development of HCC. The methylation status of SFRP1 and LINE1 genes can be used as a potentially reliable molecular marker to predict the prognosis of patients.
【作者单位】：四川大学华西基础医学与法医学院生物化学与分子生物学教研室;四川大学分析测试中心;四川大学华西医院肝血管外科;四川大学公共卫生学院卫生检验与检疫系;
【基金】：四川省科技厅科技支撑计划项目(No.2013SZ0048)资助
【分类号】：R735.7

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