血浆GSTP1和SFRP1基因甲基化分析在肝细胞癌早期诊断中的价值

摘要

Background and purpose: DNA methylation is a potential biomarker for tumor diagnosis and prognosis.This study aimed to detect the methylation statuses of GSTP1 and SFRP1 in plasma samples using a methylation-sensitive restriction enzymes-based quantitative PCR (MSRE-qPCR) method as well as to assess its clinical value for early noninvasive diagnosis of hepatocellular carcinoma (HCC).Methods: One hundred and fifty plasma samples from 72 patients with HCC, 37 patients with a benign form of the diseases and 41 normal controls were collected.The methylation statuses of GSTP1 and SFRP1 in these plasma samples were determined using the MSRE-qPCR method.Results: The methylation rates of GSTP1 and SFRP1 in HCC plasma were 54.2％ and 27.8％,respectively, which were significantly higher than those in plasma from patients with benign live diseases (9.8％ and 2.4％, P＜0.001) and normal controls patients (10.8％ and 5.4％, P＜0.001).The combination analysis of GSTP1 and SFRP1 methylation detected 63.9％ of all HCC cases.The combined analysis of using both plasma methylation and serum AFP revealed an elevated detection rate of 73.6％.Conclusion: Plasma DNA methylation analysis of GSTP1 and SFRP1 is a valuable tool for an early noninvasive diagnosis of HCC.%背景与目的:DNA甲基化是一种新的肿瘤诊断及预后判断的标志物.本研究运用自行建立的甲基化敏感性限制性内切酶一定量PCR(methylation-sensitive restriction enzymes-based quantitative PCR,MSRE-qPCR)方法检测血浆GSTP1和SFRP1基因的DNA甲基化状态,探讨其在肝细胞癌(hepatocel lular carcinoma,HCC)早期诊断中的价值.方法:收集150例血浆标本,包括72例HCC,37例肝良性病变和41名健康对照者.用MSRE-qPCR法检测血浆GSTP1和SFRP1基因DNA甲基化水平.结果:HCC患者血浆GSTP1和SFRP1甲基化阳性率分别为54.2%和27.8%,显著高于健康对照组(9.8%和2.4%,P＜0.001)和肝良性病变组(10.8%和5.4%,P＜0.001);同时检测血浆GSTP1和SFRP1可检出63.9%的HCC,而联合血清AFP分析可进一步将HCC诊断率提高至73.6%.结论:联合检测血浆GSTP1和SFRP1基因DNA甲基化对于HCC早期非侵入性诊断具有重要价值.