Background: Hepatitis B virus (HBV) infection is a major factor responsible for HBV+ hepatocellular carcinoma (HCC).
Aim: An immunological classification of HBV+ HCC may provide both biological insights and clinical implications for this disease.
Methods: Based on the enrichment of 23 immune signatures, we identified two immune-specific subtypes (Imm-H and Imm-L) of HBV+ HCC by unsupervised clustering. We showed that this subtyping method was reproducible and predictable by analyzing three different datasets.
Results: Compared to Imm-L, Imm-H displayed stronger immunity, more stromal components, lower tumor purity, lower stemness and intratumor heterogeneity, lower-level copy number alterations, higher global methylation level, and better overall and disease-free survival prognosis. Besides immune-related pathways, stromal pathways (ECM receptor interaction, focal adhesion, and regulation of actin cytoskeleton) and neuro-related pathways (neuroactive ligand-receptor interaction, and prion diseases) were more highly enriched in Imm-H than in Imm-L. We identified nine proteins differentially expressed between Imm-H and Imm-L, of which MYH11, PDCD4, Dvl3, and Syk were upregulated in Imm-H, while PCNA, Acetyl-a-Tubulin-Lys40, ER-α_pS118, Cyclin E2, and β-Catenin were upregulated in Imm-L.
Conclusion: Our data suggest that "hot" tumors have a better prognosis than "cold" tumors in HBV+ HCC and that "hot" tumors respond better to immunotherapy.
Keywords: Cancer immunotherapy; Hepatitis B virus; Hepatocellular carcinoma; Immunological classification; Transcriptomics; Tumor immunity.
©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.