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A comprehensive genome-wide profiling comparison between HBV and HCV infected hepatocellular carcinoma

机译:HBV和HCV感染的肝细胞癌的全基因组分析

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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, especially in East Asia. Even with the progress in therapy, 5-year survival rates remain unsatisfied. Chronic infection with the hepatitis B virus (HBV) or hepatitis C virus (HCV) has been epidemiologically associated with HCC and is the major etiology in the East Asian population. The detailed mechanism, especially the changes of DNA methylation and gene expression between the two types of virus-related HCC, and their contributions to the HCC development, metastasis, and recurrence remain largely unknown. In this integrated analysis, we characterized genome-scale profiles of HBV and HCV infected HCC by comparing their gene expression pattern, methylation profiles, and copy number variations from the publicly accessible data of The Cancer Genome Atlas Program (TCGA). The HLA-A, STAT1, and OAS2 genes were highly enriched and up-regulated discovered in the HCV-infected HCC. Hypomethylation but not copy number variations might be the major factor for the up-regulation of these immune-related genes in HCV-infected HCC. The results indicated the different epigenetic changes of HBV/HCV related hepatocarcinogenesis. The top up-regulated genes in HCV group were significantly clustered in the immune-related and defense response pathways. These findings will help us to understand the pathogenesis of HBV/HCV associated hepatocellular carcinoma.
机译:肝细胞癌(HCC)是全球最常见的癌症之一,尤其是在东亚。即使在治疗方面取得了进展,但5年生存率仍然不能令人满意。乙型肝炎病毒(HBV)或丙型肝炎病毒(HCV)的慢性感染与HCC在流行病学上有关,并且是东亚人群的主要病因。详细的机制,尤其是两种与病毒相关的肝癌之间的DNA甲基化和基因表达的变化,以及它们对肝癌发生,转移和复发的贡献,目前尚不清楚。在这项综合分析中,我们通过比较癌症基因组图谱计划(TCGA)可公开获得的数据,比较了它们的基因表达模式,甲基化谱图和拷贝数变异,从而表征了HBV和HCV感染的HCC的基因组规模谱。 HLA-A,STAT1和OAS2基因在HCV感染的HCC中高度富集并被上调。次甲基化而非拷贝数变异可能是HCV感染的HCC中这些免疫相关基因上调的主要因素。结果表明HBV / HCV相关肝癌发生的不同表观遗传学变化。 HCV组中最上调的基因明显聚集在免疫相关和防御反应途径中。这些发现将有助于我们了解HBV / HCV相关性肝细胞癌的发病机理。

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