Genome-wide DNA methylation analysis during non-alcoholic steatohepatitis-related multistage hepatocarcinogenesis: comparison with hepatitis virus-related carcinogenesis.
Genome-wide DNA methylation analysis during non-alcoholic steatohepatitis-related multistage hepatocarcinogenesis: comparison with hepatitis virus-related carcinogenesis.
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DOI：
10.1093/carcin/bgx005
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发表时间：
2017-03-01
期刊：
影响因子：
4.7
通讯作者：
Kanai Y
中科院分区：
文献类型：
--
作者：
Kuramoto J;Arai E;Tian Y;Funahashi N;Hiramoto M;Nammo T;Nozaki Y;Takahashi Y;Ito N;Shibuya A;Ojima H;Sukeda A;Seki Y;Kasama K;Yasuda K;Kanai Y
全基因组DNA甲基化分析表明，即使在NASH癌前阶段，DNA甲基化改变也已经存在，与病毒性肝炎或肝硬化中的这种改变明显不同，并且可能继续参与NASH相关的多期肝癌发生。本研究的目的是阐明 DNA 甲基化改变在非酒精性脂肪性肝炎 (NASH) 相关肝癌发生过程中的重要性。使用 Illumina Infinium HumanMmethylation450 BeadChip 对 264 个肝脏组织样本进行单 CpG 分辨率全基因组 DNA 甲基化分析。经过 Bonferroni 校正后，与 55 个正常肝组织 (NLT) 样本相比，3331 个探针在 113 个显示 NASH (NASH-N) 的非癌性肝组织样本中显示出显着的 DNA 甲基化改变。使用 3331 探针的主成分分析显示，NASH-N 样本的 DNA 甲基化谱与 NLT 样本和 37 个非癌性肝组织样本不同，这些样本显示与乙型肝炎病毒 (HBV) 或丙型肝炎病毒 (HCV) 感染（病毒-N）相关的慢性肝炎或肝硬化。接受者操作特征曲线分析确定了 194 个探针，它们能够将 NASH-N 样本与曲线下面积值超过 0.95 的病毒-N 样本区分开来。 Jonckheere-Terptsra趋势检验显示，非肝细胞癌（HCC）患者的NASH-N样本中的DNA甲基化改变在HCC患者的NASH-N样本中遗传或增强，然后在22个NASH相关HCC（NASH-T）样本本身中遗传或进一步增强。 NASH 和 NASH 相关的 HCC 特异性 DNA 甲基化改变在病毒 N 样本和 37 个与 HBV 或 HCV 感染相关的 HCC 样本中并不明显，但在肿瘤相关基因（如 WHSC1）中观察到，并且经常与 mRNA 表达异常相关。这些数据表明 NASH 特异性 DNA 甲基化改变可能参与 NASH 相关的多阶段肝癌发生。
Genome-wide DNA methylation analysis indicated that DNA methylation alterations are already present even at the precancerous NASH stage, clearly differing from such alterations in viral hepatitis or cirrhosis, and possibly continuing to participate in NASH-related multistage hepatocarcinogenesis. The aim of this study was to clarify the significance of DNA methylation alterations during non-alcoholic steatohepatitis (NASH)-related hepatocarcinogenesis. Single-CpG-resolution genome-wide DNA methylation analysis was performed on 264 liver tissue samples using the Illumina Infinium HumanMethylation450 BeadChip. After Bonferroni correction, 3331 probes showed significant DNA methylation alterations in 113 samples of non-cancerous liver tissue showing NASH (NASH-N) as compared with 55 samples of normal liver tissue (NLT). Principal component analysis using the 3331 probes revealed distinct DNA methylation profiles of NASH-N samples that were different from those of NLT samples and 37 samples of non-cancerous liver tissue showing chronic hepatitis or cirrhosis associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (viral-N). Receiver operating characteristic curve analysis identified 194 probes that were able to discriminate NASH-N samples from viral-N samples with area under the curve values of more than 0.95. Jonckheere-Terptsra trend test revealed that DNA methylation alterations in NASH-N samples from patients without hepatocellular carcinoma (HCC) were inherited by or strengthened in NASH-N samples from patients with HCC, and then inherited by or further strengthened in 22 samples of NASH-related HCC (NASH-T) themselves. NASH- and NASH-related HCC-specific DNA methylation alterations, which were not evident in viral-N samples and 37 samples of HCC associated with HBV or HCV infection, were observed in tumor-related genes, such as WHSC1, and were frequently associated with mRNA expression abnormalities. These data suggested that NASH-specific DNA methylation alterations may participate in NASH-related multistage hepatocarcinogenesis.
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影响因子：
6.4
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