Identification of tumor immune infiltration-associated VPS72 and prognostic significance of VPS72 and CD8A in hepatocellular carcinoma.

BACKGROUND: Copy Number Alterations (CNAs)-driven genes have gained attention as potential markers for predicting the response to immune checkpoint blockade in cancer treatment. Among them, VPS72 has emerged as a promising candidate in hepatocellular carcinoma (HCC). However, the relationship between VPS72 and immune infiltration remains unclear. METHODS: TIMER analysis was performed to identify immune populations in bulk-RNAseq data. Then, we investigated the relationship between VPS72 and immune infiltration in HCC using diverse data sources, including the TCGA and GEO databases, clinical specimens, and animal models. RESULTS: Our findings in the immunogenomic and TCGA-LIHC studies revealed significant enrichment of VPS72 among IRG in the altered group. Differential analysis and KEGG pathway analysis further highlighted the involvement of differentially expressed genes (DETs) in pathways related to the T cell receptor signaling pathway. Importantly, TIMER analysis suggested that low expression of VPS72 was associated with high infiltration of CD8 + T cells in multiple publicly available HCC datasets. To validate these findings, we conducted in vivo experiments and observed higher CD8A expression in VPS72-knockdown tumors. Additionally, in our patient cohort, individuals with low VPS72 expression exhibited higher CD8A expression. Furthermore, we identified a co-expression subtype characterized by low VPS72 and high CD8A levels, which showed a more favorable disease-free survival outcome in HCC. CONCLUSIONS: The expression of VPS72 in tumors is associated with the tumor infiltration. VPS72 and CD8A coexpression are prognostic biomarkers in HCC.