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Updated: Jul 12, 2026
Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix
Published on: October 20, 2021
HBV-infected hepatocellular carcinoma can be robustly classified into three clinically relevant subgroups by a novel
Zhiwei Cheng1,2, Leijie Li1,2, Yuening Zhang1,2
1State Key Lab of Microbial Metabolism, Joint International Research Laboratory of Metabolic Developmental Sciences, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University.
Insights
Hepatocellular carcinoma (HCC) patients infected with hepatitis B virus (HBV) can be classified into three subgroups with distinct molecular and prognostic features. This classification aids in understanding HCC progression and identifying potential diagnostic markers.
Area of Science:
- Oncology
- Hepatology
- Molecular Biology
Background:
- Liver cancer, particularly hepatocellular carcinoma (HCC), is a major global health concern.
- Hepatitis B virus (HBV) infection is a significant risk factor for HCC development.
- Robust classification of HBV-infected HCC patients is crucial for targeted treatment and improved outcomes.
Purpose of the Study:
- To classify HBV-infected HCC patients into clinically relevant subgroups.
- To investigate the molecular, immune, and prognostic characteristics of these subgroups.
- To identify potential diagnostic and prognostic markers for HBV-infected HCC.
Main Methods:
- Analysis of differentially expressed mRNAs and proteins in HBV-infected HCC patients.
- Clustering analysis to define patient subgroups (Cluster1, Cluster2, Cluster3).
- Evaluation of molecular characteristics, immune microenvironment, and survival data for each subgroup.
Main Results:
- Three distinct subgroups (Cluster1, Cluster2, Cluster3) were identified with varying molecular profiles, immune infiltration, and prognoses.
- Cluster1 showed good prognosis, low proliferation, and good immune infiltration, while Cluster3 exhibited poor prognosis, high proliferation, and poor immune microenvironment.
- Specific proteins (MCM2-7, RFC2-5, MSH2, MSH6, SMC2, SMC4, NCPAG, TOP2A) were upregulated in Cluster3, correlating with DNA repair and proliferation.
Conclusions:
- A novel classification system for HBV-infected HCC patients provides insights into disease heterogeneity.
- The identified subgroups exhibit distinct clinical and molecular features, impacting prognosis.
- Upregulated proteins in Cluster3 represent potential biomarkers for HCC diagnosis and prognosis.
Abstract:
Liver cancer is the third leading cause of cancer-related death worldwide, and hepatocellular carcinoma (HCC) accounts for a relatively large proportion of all primary liver malignancies. Among the several known risk factors, hepatitis B virus (HBV) infection is one of the important causes of HCC. In this study, we demonstrated that the HBV-infected HCC patients could be robustly classified into three clinically relevant subgroups, i.e. Cluster1, Cluster2 and Cluster3, based on consistent differentially expressed mRNAs and proteins, which showed better generalization. The proposed three subgroups showed different molecular characteristics, immune microenvironment and prognostic survival characteristics. The Cluster1 subgroup had near-normal levels of metabolism-related proteins, low proliferation activity and good immune infiltration, which were associated with its good liver function, smaller tumor size, good prognosis, low alpha-fetoprotein (AFP) levels and lower clinical stage. In contrast, the Cluster3 subgroup had the lowest levels of metabolism-related proteins, which corresponded with its severe liver dysfunction. Also, high proliferation activity and poor immune microenvironment in Cluster3 subgroup were associated with its poor prognosis, larger tumor size, high AFP levels, high incidence of tumor thrombus and higher clinical stage. The characteristics of the Cluster2 subgroup were between the Cluster1 and Cluster3 groups. In addition, MCM2-7, RFC2-5, MSH2, MSH6, SMC2, SMC4, NCPAG and TOP2A proteins were significantly upregulated in the Cluster3 subgroup. Meanwhile, abnormally high phosphorylation levels of these proteins were associated with high levels of DNA repair, telomere maintenance and proliferative features. Therefore, these proteins could be identified as potential diagnostic and prognostic markers. In general, our research provided a novel analytical protocol and insights for the robust classification, treatment and prevention of HBV-infected HCC.
