Pan-cancer analyses reveal the genetic and pharmacogenomic landscape of transient receptor potential channels

Abstract

Abstract Transient-receptor potential (TRP) channels comprise a diverse family of ion channels, which play important roles in regulation of intracellular calcium. Emerging evidence has revealed the critical roles of TRP channels in tumor development and progression. However, we still lack knowledge about the genetic and pharmacogenomics landscape of TRP genes across cancer types. Here, we comprehensively characterized the genetic and transcriptome alterations of TRP genes across >10,000 patients of 33 cancer types. We revealed prevalent somatic mutations and copy number variation in TRP genes. In particular, mutations located in transmembrane regions of TRP genes were likely to be deleterious mutations (p-values < 0.001). Genetic alterations were correlated with transcriptome dysregulation of TRP genes, and we found that TRPM2, TRPM8, and TPRA1 showed extent dysregulation in cancer. Patients with TRP gene alterations were with significantly higher hypoxia scores, tumor mutation burdens, tumor stages and grades, and poor survival. The alterations of TRP genes were significantly associated with the activity of cancer-related pathways. Moreover, we found that the expression of TRP genes were potentially useful for development of targeted therapies. Our study provided the landscape of genomic and transcriptomic alterations of TPRs across 33 cancer types, which is a comprehensive resource for guiding both mechanistic and therapeutic analyses of the roles of TRP genes in cancer. Identifying the TRP genes with extensive genetic alterations will directly contribute to cancer therapy in the context of predictive, preventive, and personalized medicine.