Published online Dec 15, 2023. doi: 10.4251/wjgo.v15.i12.2064
Peer-review started: July 6, 2023
First decision: October 9, 2023
Revised: October 17, 2023
Accepted: November 10, 2023
Article in press: November 10, 2023
Published online: December 15, 2023
The most typical form of primary liver cancer is hepatocellular carcinoma (HCC). People with chronic liver conditions, such as cirrhosis caused by hepatitis B or hepatitis C infection, are most likely to develop HCC. Although the predictive value of TRP-related genes in HCC is unknown, transient receptor potential (TRP) family gene proteins influence tumor progression. Our current study aimed to assess the family-related TRP factors to establish the prognosis and treatment plan for HCC. We downloaded the mRNA expression profiles and corresponding clinical information for the HCC patients from the cancer genome atlas (TCGA) database. Univariate and least absolute contraction and selection operator (LASSO) Cox regression models were used to construct the TRP risk spectrum, infer the clinically significant TRP family core genes, and examine the correlation between the core gene TRP canonical type 1 (TRPC1) and the expression and prognosis of HCC. Our findings propose that the predictive characteristics of the 3-TRP gene discussed in this study are not only effective for prognosis prediction but also related to the tumor's immune status and the infiltration of various immune cells in the tumor microenvironment. These results may provide significant clinical indications for HCC patients to propose a new combination therapy consisting of targeted anti-TRP treatment and immunotherapy.
To investigate the role of TRP genes in HCC, their association with HCC development and treatment was examined.
To investigate the role of TRP genes in HCC, their association with HCC development and treatment was examined.
HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database, and univariate and LASSO 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 TRPC1 gene and HCC patient prognosis was evaluated.
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.
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.
In the future, we will focus on in-depth studies on the mechanism of how TRPC1 regulates the development of HCC.