Identification of molecular subtypes and prognostic signatures based on transient receptor potential channel-related genes to predict the prognostic risk of hepatocellular carcinoma

Abstract

Objective: Abnormal transient receptor potential (TRP) channel function interferes with intracellular calcium-based signaling and causes malignant phenotypes. However, effects of TRP channel-related genes on hepatocellular carcinoma (HCC) remain unknown. This study aimed to identify HCC molecular subtypes and prognostic signatures based on TRP channel-related genes to predict its prognostic risks. Methods: With the expression data of TRP channel-related genes, unsupervised hierarchical clustering was applied to identify HCC molecular subtypes, followed by comparisons of clinical and immune microenvironment characteristics between the resulting subtypes. After screening differentially expressed genes (DEGs) among subtypes, prognostic signatures were identified to construct risk score-based prognostic and nomogram models and predict HCC survival. Finally, tumor drug sensitivities were predicted and compared between risk groups. Results: Sixteen TRP channel-related genes that were differentially expressed between HCC and normal tissues were used to identify two subtypes, of which cluster 1 had higher TRP scores, better survival status, and lower levels of clinical malignancy. Immune-related analyses also revealed higher infiltrations of M1 macrophages and immune and stromal scores in cluster 1 compared with cluster 2. After screening DEGs between subtypes, six prognostic signatures were identified to construct prognostic and nomogram models. The potential of these models for assessing HCC prognostic risks was further validated. Furthermore, cluster 1 was more distributed in the low-risk group with higher drug sensitivities. Conclusion: Two HCC subtypes were identified, among which cluster 1 was associated with a favorable prognosis. Prognostic signatures related to TRP channel genes and molecular subtypes can predict HCC prognostic risks.