Abstract
BackgroundTransient 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.MethodsWe 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.ResultsExtensive 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.ConclusionThis 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.
Highlights
The discovery of a new superfamily of channels called ‘transient receptor potential’ (TRP) channels has been described in the last two decades
TRPV6 was markedly up-regulated in the pancreas and prostate, while TRPV2 was overexpressed in the blood, lung, and spleen (Figure 1A)
TRPV5 and TRPV6 were down-regulated in most cancers, while TRPV2 and TRPV3 tend to be up-regulated in most cases
Summary
The discovery of a new superfamily of channels called ‘transient receptor potential’ (TRP) channels has been described in the last two decades. These channels mediate calcium (Ca2+) ions entry into cells. TRP vanilloid (TRPV) channels are the main players in nociception and integration of pain signals [5]. Recent studies showed that family members of TRPV channels play a vital important role in different cancers [6,7,8,9]. 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
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