MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma
MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma
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MT1M 和 MT1G 启动子甲基化作为肝细胞癌的生物标志物
DOI：
10.3748/wjg.v20.i16.4723
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发表时间：
2014-04-28
影响因子：
4.3
通讯作者：
Wang, Kai
中科院分区：
文献类型：
--
作者：
Ji, Xiang-Fen;Fan, Yu-Chen;Wang, Kai
目的：探讨两种肿瘤抑制基因（TSGs）启动子甲基化作为肝细胞癌（HCC）生物标志物的潜力。方法：本回顾性队列共纳入189名受试者，其中121名无治愈史的HCC患者，37名慢性乙型肝炎（CHB）患者和31名正常对照（nc）。从每个受试者400 μ L的血清中提取DNA样本，然后用亚硫酸氢盐处理。利用甲基化特异性聚合酶链反应测定TSGs启动子（金属硫蛋白1M， MT1M和金属硫蛋白1G， MT1G）的甲基化。结合MT1M和MT1G启动子甲基化的诊断价值用受试者工作特征曲线下面积评价。结果：HCC组血清MT1M（48.8%, 59/121）和MT1G（70.2%, 85/121）启动子甲基化状态显著高于CHB组（MT1M 5.4%, 2/37, P < 0.001; MT1G 16.2%, 6/37, P < 0.001）和NC组（MT1M 6.5%, 2/31, P < 0.001; MT1G 12.9%, 4/27, P < 0.001）。异常的血清MT1M启动子甲基化具有更高的区分HCC与CHB（94.6%）和nc（93.5%）的特异性，而血清MT1M和MT1G启动子甲基化联合具有更高的诊断敏感性（90.9%），表明它们是HCC无创检测的潜在标志物。MT1M启动子甲基化与肿瘤大小呈正相关（rs = 0.321, P < 0.001）， MT1M和MT1G启动子甲基化的HCC患者血管侵犯或转移的发生率更高（P = 0.018）。结论：MT1M和MT1G启动子甲基化可作为HCC无创检测的血清生物标志物。（三）2014年百世登出版集团有限公司版权所有。
AIM: To investigate the potential of promoter methylation of two tumor suppressor genes (TSGs) as biomarkers for hepatocellular carcinoma (HCC).METHODS: A total of 189 subjects were included in this retrospective cohort, which contained 121 HCC patients without any history of curative treatment, 37 patients with chronic hepatitis B (CHB), and 31 normal controls (NCs). DNA samples were extracted from 400 mu L of serum of each subject and then modified using bisulfite treatment. Methylation of the promoters of the TSGs (metallothionein 1M, MT1M; and metallothionein 1G, MT1G) was determined using methylation-specific polymerase chain reaction. The diagnostic value of combined MT1M and MT1G promoter methylation was evaluated using the area under the receiver operating characteristic curves.RESULTS: Our results indicated that the methylation status of serum MT1M (48.8%, 59/121) and MT1G (70.2%, 85/121) promoters in the HCC group was significantly higher than that in the CHB group (MT1M 5.4%, 2/37, P < 0.001; MT1G 16.2%, 6/37, P < 0.001) and NC group (MT1M 6.5%, 2/31, P < 0.001; MT1G 12.9%, 4/27, P < 0.001). Aberrant serum MT1M promoter methylation gave higher specificity to discriminate HCC from CHB (94.6%) and NCs (93.5%), whereas combined methylation of serum MT1M and MT1G promoters showed higher diagnostic sensitivity (90.9%), suggesting that they are potential markers for noninvasive detection of HCC. Furthermore, MT1M promoter methylation was positively correlated with tumor size (rs = 0.321, P < 0.001), and HCC patients with both MT1M and MT1G promoter methylation tended to show a higher incidence of vascular invasion or metastasis (P = 0.018).CONCLUSION: MT1M and MT1G promoter methylation may be used as serum biomarkers for noninvasive detection of HCC. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.