Promoter hypermethylation of TERT is associated with hepatocellular carcinoma in the Han Chinese population
Promoter hypermethylation of TERT is associated with hepatocellular carcinoma in the Han Chinese population
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TERT启动子高甲基化与中国汉族人群的肝细胞癌相关
DOI：
10.1016/j.clinre.2015.01.002
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发表时间：
2015-10-01
影响因子：
2.7
通讯作者：
Liu, Yun
中科院分区：
文献类型：
--
作者：
Zhang, Hong;Weng, Xiaoling;Liu, Yun
背景资料：在转录起始位点（UTSS）上游，端粒酶逆转录酶（TERT）基因的超甲基化已被证明与儿科脑肿瘤的肿瘤进展和不良预后相关（Castelo-Branco 2013）。已经推断，TERT的UTSS区域是各种癌症的潜在可获得的生物标志物。在这项研究中，我们的目的是探讨端粒酶在肝细胞癌（HCC）中的作用，并探讨是否在端粒酶启动子的UTSS区域显示相同的甲基化模式在HCC.Methods：我们分析了结果的甲基化检测端粒酶，包括UTSS区域，从125对肝癌样本使用大规模阵列EpiTyper（Sequenom，圣地亚哥，加利福尼亚州，美国）。为了确定TERT启动子甲基化状态和TERT表达水平之间的关系，我们分析了一个验证组的12个配对的HCC样本，并获得了FPKM值为TERTgene.Results：我们的结果显示，异常甲基化的端粒酶启动子的UTSS区域在HCC（平均值= 15.1）与相邻的正常组织（平均值= 6.1，P < 0.00001）相比。结论：肝癌组织中高甲基化与TERT高表达呈正相关，提示TERT可能参与了肝癌的发病机制。我们的研究结果表明，未来的研究可能是富有成效的。(C)2015年Elsevier Masson SAS。All rights reserved.
Background: Upstream of the transcription start site (UTSS), hypermethylation of the telomerase reverse transcriptase (TERT) gene has been shown to be associated with tumour progression and a poor prognosis in paediatric brain tumours (Castelo-Branco 2013). It has been inferred that the UTSS region of TERT is a potentially accessible biomarker for various cancers. In this study, we aimed to explore the role of TERT in hepatocellular carcinoma (HCC) and to investigate whether the UTSS region of the TERT promoter shows the same methylation pattern in HCC.Methods: We analysed the results of a methylation assay for TERT, including the UTSS region, from 125 paired HCC samples using Mass Array EpiTyper (Sequenom, San Diego, CA, USA). To determine the relationship between TERT promoter methylation status and the TERT expression level, we analysed a validation group of 12 paired HCC samples and acquired the FPKM values for the TERT gene.Results: Our results showed aberrant methylation of the UTSS region of the TERT promoter in HCC (mean = 15.1) compared with the adjacent normal tissues (mean = 6.1, P < 0.00001). Furthermore, a nearly 56-fold increase in TERT expression from the hypermethylated promoter was found in HCC (P < 0.05), indicating a positive relationship between TERT methylation and expression.Conclusions: As hypermethylation was positively correlated with high expression of TERT in HCC, TERT is likely to be involved in the aetiology of HCC. Our findings indicate that future studies on TERT might be fruitful. (C) 2015 Elsevier Masson SAS. All rights reserved.