A comprehensive genome-wide profiling comparison between HBV and HCV infected hepatocellular carcinoma
A comprehensive genome-wide profiling comparison between HBV and HCV infected hepatocellular carcinoma
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HBV 和 HCV 感染的肝细胞癌之间全面的全基因组分析比较
DOI：
10.1186/s12920-019-0580-x
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发表时间：
2019-10-28
影响因子：
2.7
通讯作者：
Li, Xiaofang
中科院分区：
文献类型：
--
作者：
Sun, Suofeng;Li, Yuan;Li, Xiaofang
肝细胞癌（HCC）是世界范围内最常见的癌症之一，特别是在东亚地区。即使在治疗方面取得进展，5年生存率仍然不令人满意。慢性乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染在流行病学上与HCC相关，并且是东亚人群的主要病因。详细的机制，特别是DNA甲基化和基因表达在两种类型的病毒相关性HCC之间的变化，以及它们在HCC的发生、转移和复发中的作用在很大程度上仍然未知。方法在这项综合分析中，我们通过比较来自癌症基因组图谱计划（TCGA）的公开数据，HBV和HCV感染HCC的基因表达模式、甲基化谱和拷贝数变化，来表征HBV和HCV感染HCC的基因组尺度谱。结果在hcv感染的HCC中发现HLA-A、STAT1和OAS2基因高度富集和上调。低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。结论HBV/HCV相关肝癌发生存在不同的表观遗传变化。HCV组高表达基因在免疫相关通路和防御反应通路上显著聚集。这些发现将有助于我们了解HBV/HCV相关肝细胞癌的发病机制。
BackgroundHepatocellular 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.MethodsIn 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).ResultsThe 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.ConclusionsThe 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.