Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, especially in East Asia
The East Asian neonatal vaccination program has resulted in a tremendous decrease (70–85%) of the incidence of hepatitis B virus (HBV)-related HCC [10]
Our results showed a substantial difference of hepatocarcinogenesis between the HBV and hepatitis C virus (HCV) infected HCC and the results improve our understanding of the molecular landscape of HCC
Summary
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, especially in East Asia. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is the most common cause of death in people with cirrhosis [1]. Worldwide, this cancer is the third leading cause of cancer-related deaths, leading to about 1 million deaths annually [2]. 5-year survival rates of HCC remain unfavorable. The East Asian neonatal vaccination program has resulted in a tremendous decrease (70–85%) of the incidence of HBV-related HCC [10]. A better understanding of the underlying biological mechanisms involved in HCC pathogenesis and progression is critical for the development of novel diagnostic biomarkers and therapeutic strategies
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