ArticleHuman genomics2025
TRP channels in hepatocellular carcinoma: integrative Mendelian randomization and multi-omics analyses highlight MCOLN3/TRPV4 as candidate dual-effect biomarkers.
Article in Human genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Cannabidiol-Ion Channel Interactions Represent a Promising Preventive and Therapeutic Strategy in Hepatocellular Carcinoma.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
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3 authors.
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Abstract
backgroundThe causal relationship between Transient receptor potential (TRP) and hepatocellular carcinoma (HCC) remains unclear. Our study aimed to identify potential drug targets for HCC within the TRP family using Mendelian randomization (MR).
methodsThe gene expression quantitative trait loci (eQTL) data for TRP was sourced from eQTLGen Consortium. Summary statistics for HCC came from European (nCase = 379, nControl = 475,259) and East Asian population (nCase = 2122, nControl = 159,201). We undertook main MR analysis in the European population using the R package 'TwosampleMR', with significance determined through Bonferroni correction. The East Asian population serves as the validation cohort. Sensitivity analyses include Steiger filtering, bidirectional MR analysis, multivariable MR (MVMR) analysis, and phenotype scanning for further validation of causal relationships.
resultsMain MR analysis had identified two causal TRPs, MCOLN3 (OR = 1.59, 95% CI: 1.24-2.06) and TRPV4 (OR = 0.597, 95% CI: 0.407-0.875). No heterogeneity or pleiotropy was detected. The basal metabolic rate may partially mediate the causal effect of TRPV4 on HCC. Drugs such as cisplatin and Cannabidiol were identified for their potential action on causal TRPs. High expression of MCOLN3 may lead to increased sensitivity to sorafenib, while patients with low expression of MCOLN3 and TRPV4 were more likely to benefit from immunotherapy. Furthermore, we revealed the expression landscape of causal TRPs in HCC by performing integrated multi-omics analyses.
conclusionsThis MR analysis revealed a causal relationship between TRP and HCC, and MCOLN3 and TRPV4 were potential drug targets. They also served as potential molecular biomarkers for the efficacy of immunotherapy and/or targeted therapy, providing a strong theoretical basis for the clinical application of TRPs.
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