School of Medicine Publications

Document Type

Article

Publication Date

3-27-2026

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Comments

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 

Publication Title

Discover Oncology

DOI

10.1007/s12672-026-04744-4

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology

Included in

Oncology Commons

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