Bioinformatics analysis of TRPV1 expression and its role in hepatocellular carcinoma prognosis

Hepatocellular carcinoma (HCC) is among the most lethal malignancies globally, with a persistently poor prognosis due to late diagnosis and limited therapeutic options available. The transient receptor potential vanilloid 1 (TRPV1), a calcium-permeable cation channel, plays critical roles in cancer pathogenesis across several cancer types, but its role in HCC remains poorly defined. We performed an integrative bioinformatics analysis of TRPV1 utilizing multiple public databases, including TCGA, GEO, TIMER, UALCAN, cBioPortal, LinkedOmics, and COSMIC in HCC. We examined the TRPV1 expression profile, prognostic significance, genetic alterations, DNA methylation status, co-expression networks, and correlations with immune infiltration. Single-cell RNA sequencing and drug sensitivity dataset analyses offered additional insights into its potential functional exploration. TRPV1 mRNA expression was upregulated in HCC and correlated with multiple clinicopathological features. The high expression of TRPV1 is associated with better prognostic significance for OS, DFS, DSS, and DFI. Genetic alterations in TRPV1 occurred in 6% of tumors, mostly missense mutations (16.16%). Its expression negatively correlated with promoter methylation levels. The functional enrichment analyses demonstrate an association between TRPV1 and metabolic pathways, such as vitamin D metabolism, nicotine degradation, and biosynthesis of arginine. We also found that TRPV1 was positively associated with CD4⁺ T cell infiltration but negatively correlated with CD8⁺ T cells, B cells, dendritic cells, and macrophages. Furthermore, single-cell analysis demonstrates that malignant cells and fibroblasts have predominant TRPV1 expression. Drug sensitivity profiling demonstrates a significant association of TRPV1 with multiple CTRP drugs. In this study, we identified TRPV1 as a promising prognostic biomarker in HCC, associated with favorable clinical outcomes and distinct immune landscape characteristics, and a potential therapeutic target. Further mechanistic validation and clinical investigation are needed.