Integrated Analysis of PSMB8 Expression and Its Potential Roles in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) represents a highly aggressive malignancy with significant global health implications. The proteasome subunit beta type-8 (PSMB8) gene, known for its association with hepatitis B virus susceptibility, has emerged as a potential regulator of tumor progression. However, its functional role and clinical significance in HCC remain poorly characterized.

We conducted a comprehensive multi-omics analysis to elucidate the role of PSMB8 in HCC. PSMB8 expression profiles were derived from The Cancer Genome Atlas and validated using the GSE76427 dataset. Prognostic significance was assessed through Kaplan-Meier survival analysis. Then, we systematically evaluated the relationships between PSMB8 expression and clinicopathological features, somatic mutations, immune cell infiltration, immune regulatory genes, and immune checkpoint responses. Single-cell RNA sequencing data from the Tumor Immune Single-cell Hub database were analyzed to determine cell type-specific PSMB8 expression. Tissue-level validation was performed using multiplex immunofluorescence staining on HCC tissue microarrays.

PSMB8 demonstrated significant overexpression in HCC tissues and exhibited strong prognostic value. Single-cell analysis revealed predominant PSMB8 expression in T and B cell populations. Notably, PSMB8 expression showed significant positive correlations with immune checkpoint molecules PD-L1/CD274 and CD27. Functional enrichment analysis implicated PSMB8 in multiple oncogenic pathways, particularly proteasome-related processes.

Our findings position PSMB8 as a promising prognostic biomarker and potential therapeutic target in HCC. The observed associations with immune checkpoint molecules and proteasomal pathways suggest its potential role in modulating tumor immunity and protein homeostasis, warranting further investigation into its mechanistic contributions to HCC progression.