肝细胞癌血浆LINE-1启动子区甲基化水平的研究

Research of methylation of the LINE-1 promoter in peripheral plasma of hepatocellular carcinoma

目的探讨肝细胞癌(HCC)患者血浆中长散布核元件-1(LINE-1)基因启动子区CpG位点甲基化水平变化的临床意义。方法应用亚硫酸氢盐测序PCR(BSP)检测33例HCC患者(HCC组)、18例肝硬化患者(肝硬化组)及16例健康志愿者(正常组)的外周血血浆中LINE-1启动子区的CpG位点甲基化程度。结果 HCC组的LINE-1启动子区多个CpG位点甲基化水平及整体甲基化水平下降;进一步通过ROC曲线分析发现CpG位点1、位点7、位点8的甲基化水平对诊断HCC的能力较优,其敏感度和特异度分别为80.0%和78.8%、81.8%和71.4%、82.9%和75.8%。结论 LINE-1基因启动子区甲基化水平在HCC中明显下降,其中CpG位点1、位点7、位点8的甲基化水平可能对HCC诊断有意义。

Objective To investigate the change of methylation levels of the long interspersed nucleotide acids element-1 （LINE-1） promotor by using bisulfite sequencing PCR （BSP） in peripheral plasma of hepatocellular carcinoma （HCC）. Methods BSP method was used to detect the methylation levels of the LINE-1 promotor in 67 plasma samples from 33 cases of HCC （ HCC group）, 18 cases of cirrhosis （cirrhosis group） and 16 healthy volunteers （normal group）. Results The results of BSP showed that methylation levels of the LINE-1 promotor in patients with HCC were significantly lower than those in cirrhosis group and normal group （ P 〈 0. 05 ）. The receiver-operating characteristic curve analysis of methylation of some CpG sites（ site 1, site 7, site 8 ） in the LINE- 1 promotor revealed an important diagnostic efficacy for HCC, and the sensitivity and specificity of the site 1, site 7, site 8 were 80. 0% and 78.8% , 81.8% and 71.4% , 82. 9% and 75.8% , respectively. Conclusion The promotor of LINE-1 has hypomethylation in HCC, and methylation of some CpG sites（ site 1, site 7, site 8 ） in [ Key Words ]