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Updated: Jan 4, 2026

Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma
Published on: April 25, 2025
A comprehensive genome-wide profiling comparison between HBV and HCV infected hepatocellular carcinoma
Suofeng Sun1, Yuan Li2, Shuangyin Han1
1Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, China.
Insights
Hepatocellular carcinoma (HCC) differs between hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. HCV-related HCC shows distinct epigenetic changes, particularly in immune-related genes, impacting cancer development.
Area of Science:
- Oncology
- Virology
- Epigenetics
Background:
- Hepatocellular carcinoma (HCC) is a prevalent cancer globally, with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections being major causes, especially in East Asia.
- Despite therapeutic advancements, HCC survival rates remain suboptimal, and the precise molecular mechanisms, including epigenetic alterations, driving HBV/HCV-related HCC are not fully understood.
Purpose of the Study:
- To compare the genome-scale molecular profiles of HBV- and HCV-infected HCC.
- To elucidate the distinct epigenetic changes, gene expression patterns, and copy number variations in HBV- versus HCV-related hepatocellular carcinoma.
Main Methods:
- Integrated analysis of publicly available The Cancer Genome Atlas Program (TCGA) data.
- Comparative analysis of gene expression, DNA methylation, and copy number variations between HBV- and HCV-infected HCC cohorts.
Main Results:
- HCV-infected HCC exhibited significant enrichment and up-regulation of immune-related genes, including HLA-A, STAT1, and OAS2.
- Hypomethylation, rather than copy number variations, was identified as a key factor contributing to the up-regulation of these immune genes in HCV-related HCC.
Conclusions:
- HBV and HCV infections induce distinct epigenetic modifications during hepatocarcinogenesis.
- The identified molecular differences, particularly in immune response pathways, enhance understanding of the pathogenesis of HBV/HCV-associated HCC.
Background:
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.
Methods:
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).
Results:
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.
Conclusions:
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.

