Uncovering core stemness biomarkers in HBV-HCC through integrated multi-omics

Area of Science:

• Hepatology and Cancer Research
• Genomics and Bioinformatics

Background:

• Chronic hepatitis B virus (HBV) infection is a primary cause of liver cancer (HCC).
• Cancer stem cells (CSCs) drive tumor growth and treatment resistance in HBV-associated HCC (HBV-HCC).
• Mechanisms linking HBV infection to stemness in HBV-HCC are not fully understood.

Purpose of the Study:

• To identify novel molecular regulators of stemness in HBV-HCC.
• To discover potential diagnostic and prognostic biomarkers for HBV-HCC.
• To explore therapeutic strategies targeting stemness pathways in HBV-HCC.

Main Methods:

• Integrated in silico multi-omics analysis of single-cell and bulk transcriptomic data.
• Stemness scoring, pseudotime trajectory, and CytoTRACE2 analysis of single-cell RNA sequencing (scRNA-seq) data.
• Weighted gene co-expression network analysis (WGCNA) and Random Forest feature selection on bulk RNA sequencing (bulk RNA-seq) data.

Main Results:

• Endothelial cells were identified as a key cell population associated with stemness.
• Two high-confidence biomarkers, SSR2 and UBE2D3, were prioritized.
• A diagnostic model using SSR2 and UBE2D3 demonstrated favorable performance and prognostic value.
• SSR2 and UBE2D3 are linked to endoplasmic reticulum stress and mTOR signaling.

Conclusions:

• SSR2 and UBE2D3 are proposed as candidate diagnostic and prognostic biomarkers for HBV-HCC.
• These biomarkers may play a role in viral persistence and stemness maintenance.
• Findings provide a framework for developing targeted therapies against HBV-HCC.