Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients

Abstract

BACKGROUND Members of the transient receptor potential (TRP) protein family shape oncogenic development, but the specific relevance of TRP-related genes in hepatocellular carcinoma (HCC) has yet to be defined. AIM To investigate the role of TRP genes in HCC, their association with HCC development and treatment was examined. METHODS HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database, and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum. Based on these analyses, clinically relevant TRP family genes were selected, and the association between the key TRP canonical type 1 (TRPC1) gene and HCC patient prognosis was evaluated. RESULTS In total, 28 TRP family genes were screened for clinical relevance, with multivariate analyses ultimately revealing three of these genes (TRPC1, TRP cation channel subfamily M member 2, and TRP cation channel subfamily M member 6) to be significantly associated with HCC patient prognosis (P < 0.05). These genes were utilized to establish a TRP-related risk model. Patients were separated into low- and high-risk groups based on the expression of these genes, and high-risk patients exhibited a significantly poorer prognosis (P = 0.001). Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways. TRPC1 was identified as a candidate gene in this family worthy of further study, with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes. Consistently, quantitative, immunohistochemistry, and western blot analyses revealed increased TRPC1 expression in HCC. CONCLUSION These three TRP genes help determine HCC patient prognosis, providing insight into tumor immune status and immunological composition. These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.