Pan-Cancer Analysis Reveals Genomic and Clinical Characteristics of TRPV Channel-Related Genes

Abstract

Background: Transient Receptor Potential channels (TRPs), a class of ion channels, were first described two decades ago. Many TRP family members are major participants in nociception and integration of heat and pain signals. Recent studies have revealed that subfamilies of this channel, such as members of transient receptor potential vanilloid (TRPV) channels, play important roles in breast, ovarian, prostate, and pancreatic cancers. Methods: We performed a comprehensive analysis of TRPVs in 9125 tumor samples of 33 cancer types using multi-omics data extracted from The Cancer Genome Atlas (TCGA). We identified differences in mRNA expression in a pan-cancer analysis, and the genomic characteristics of single nucleotide variations, copy number variations, methylation features, and miRNA–mRNA interactions using data from TCGA. Finally, we evaluated the sensitivity and resistance to drugs targeting TRPV channel-related genes using the Cancer Therapeutics Response Portal (CTRP) and the Genomics of Drug Sensitivity in Cancer (GDSC) database. Finally, we validated the drug sensitive data and the importance of TRPV6 in two cancer cell lines using q-PCR assay, CCK8 assay, EdU assay and scratch assay. Results: Extensive genetic alterations in TRPV channel-related genes and differences in gene expression were associated with the activity of cancer marker-related pathways. TRPV channel-related genes can be used as prognostic biomarkers. Several potential drugs, such as lapatinib, that may target TRPV channel-related genes were identified by mining the genomics of drug sensitivity. Conclusion: This study revealed the genomic changes and clinical characteristics of TRPV channel-related regulatory factors in 33 types of tumors. This analysis may help uncover the TRPV channel-related genes associated with tumorigenesis. We also proposed novel strategies for tumor treatment.