Abstract
Background: Transient receptor potential cation channel subfamily V member 4 (TRPV4) has been reported to regulate tumor progression in many tumor types. However, its association with the tumor immune microenvironment remains unclear. Methods: TRPV4 expression was assessed using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The clinical features and prognostic roles of TRPV4 were assessed using TCGA cohort. Gene set enrichment analysis (GSEA) of TRPV4 was conducted using the R package clusterProfiler. We analyzed the association between TRPV4 and immune cell infiltration scores of TCGA samples downloaded from published articles and the TIMER2 database. The IC50 values of 192 anti-cancer drugs were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database and the correlation analysis was performed. Results: TRPV4 was highly expressed and associated with worse overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in colon adenocarcinoma (COAD) and ovarian cancer. Furthermore, TRPV4 expression was closely associated with immune regulation-related pathways. Moreover, tumor-associated macrophage (TAM) infiltration levels were positively correlated with TRPV4 expression in TCGA pan-cancer samples. Immunosuppressive genes such as PD-L1, PD-1, CTLA4, LAG3, TIGIT, TGFB1, and TGFBR1 were positively correlated with TRPV4 expression in most tumors. In addition, patients with high expression of TRPV4 might be resistant to the treatment of Cisplatin and Oxaliplatin. Conclusion: Our results suggest that TRPV4 is an oncogene and a prognostic marker in COAD and ovarian cancer. High TRPV4 expression is associated with tumor immunosuppressive status and may contribute to TAM infiltration based on TCGA data from pan-cancer samples. Patients with high expression of TRPV4 might be resistant to the treatment of Cisplatin and Oxaliplatin.
Highlights
Transient receptor potential cation channel subfamily V member 4 (TRPV4) has been reported to regulate tumor progression in many tumor types
We found that TRPV4 was overexpressed in 19 cancer types, namely, bladder urothelial carcinoma (BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), lymphoid neoplasm diffuse large B-cell lymphoma (DLBCL), esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), brain low-grade glioma (LGG), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), ovarian serous cystadenocarcinoma, pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), testicular germ cell tumors (TGCTs), thymoma (THYM), uterine corpus endometrial carcinoma (UCEC), and uterine carcinosarcoma (UCS)
Low TRPV4 expression was observed in only six cancer types, namely, adrenocortical carcinoma (ACC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), prostate adenocarcinoma (PRAD), skin cutaneous melanoma (SKCM), and thyroid carcinoma (THCA) (Figure 1A)
Summary
Transient receptor potential cation channel subfamily V member 4 (TRPV4) has been reported to regulate tumor progression in many tumor types. TRPV4 is a broadly expressed polymodally activated ion channel. It is reported to be involved in tumor progression in several tumor types, playing different or even opposite roles therein. Overexpression of TRPV4 promotes epithelial to mesenchymal transition in breast cancer cells (Huang et al., 2021). TRPV4 promotes metastasis of endometrial cancer cells by regulating the RhoA/ROCK1 pathway (Li et al, 2020). TRPV4 activation inhibits glioma progression (Huang et al, 2021). Despite these reports, the role of TRPV4 in most tumor types remains unclear
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