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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(P<0.05);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。
Objective To investigate the relationship between the secretory curl-associated protein (SFRP) 1 and the methylation of CpG island in the promoter region of LINE 1 gene and the clinicopathologic parameters of human primary hepatocellular carcinoma (HCC) The significance of the assessment. Methods The plasma DNA of 105 HCC patients and 50 healthy controls were collected. Methylation-specific PCR (MSP) was used to detect the hypermethylation of CpG island in promoter region of SFRP1 gene and hypomethylation of CpG island in promoter region of LINE1 gene The relationship between the methylation status of two gene promoters and the clinicopathological parameters of HCC patients was analyzed. The methylation status of SFRP1 and LINE1 genes was analyzed by Kaplan-Meier curve, log-rank test and Cox multivariate analysis. The relationship between overall survival and disease-free survival. Results The positive rate of hypermethylation of CpG island in promoter region of SFRP1 gene was 59.05% (62/105) in 105 patients with liver cancer. The methylation rate of CpG island in promoter region of LINE1 gene was 66.67% (70/105), SFRP1 The methylation status of hypermethylation and LINE1 hypomethylation was 43.81% (46/105). No methylation of these two genes was found in the normal control group. Whether hypermethylation of SFRP1 and hypomethylation of LINE1 was positive with HBsAg and (P <0.05). The methylation status of SFRP1 and LINE1 gene promoters was related to overall survival and disease-free survival rate. Patients with hypermethylated SFRP1 + low methylation-negative LINE1 The prognosis is best, while SFRP1 hypermethylation + LINE1 hypomethylation patients have the worst prognosis. Conclusion The methylation status of CpG island in SFRP1 and LINE1 gene promoters is related to the occurrence and development of hepatocellular carcinoma. The methylation status of SFRP1 and LINE1 genes can be used as a potentially reliable molecular marker to predict the prognosis of patients.