Multi-Omics Analysis of the Prognosis and Biological Function for TRPV Channel Family in Clear Cell Renal Cell Carcinoma

Abstract

BackgroundThe transient receptor potential vanilloid (TRPV) channels family, TRPV1-6, has been identified to profoundly affect a wide spectrum of pathological processes in various cancers. However, the biological function and prognostic value of TRPVs in clear cell renal cell carcinoma (ccRCC) are still largely unknown.MethodsWe obtained the gene expression data and clinical information of 539 ccRCC patients from The Cancer Genome Atlas (TCGA) database. A series of databases were used for data processing and visualization, including GEPIA, GeneMANIA, MethSurv, GSCA, TIMER, and starBase databases.ResultsThe mRNA expression of TRPV2/3 was upregulated while the expression of TRPV5/6 was downregulated in ccRCC tumor tissues. TRPV family members in ccRCC were rarely mutated (nearly 7 frequencies). The ROC curve showed that TRPV2/5/6 had a high diagnostic ability in discriminating ccRCC from the control samples (AUC>0.9). Higher levels of TRPV3 expression were associated with poor prognosis of ccRCC patients, while higher expression of TRPV4 was associated with favorable prognosis. The expression of TRPV3 in normal and ccRCC tissues was validated by Immunohistochemistry, and its expression was remarkably related to high histologic grade and advanced stage. Besides, TRPV3 exhibit a reduction of DNA methylation level with tumor progression, and 12 CpGs of TRPV3 were associated with a significant prognosis. In addition, TRPV3 expression was significantly associated with the accumulation of several tumor-infiltrating immune cells, especially regulatory T cells. Furthermore, high levels of TRPV3 induced the expression of immune checkpoints such as LAG3, CTLA4, PDCD1, and TIGIT. Finally, we predicted a key SNHG3/AL513497.1-miR-10b-5p-TRPV3 axis linking to carcinogenesis and progression of ccRCC.ConclusionOur study may uncover TRPV channels–associated molecular mechanisms involved in the tumorigenesis and progression of ccRCC. TRPV family members might be diagnosed and prognostic markers and potential therapeutic targets for ccRCC patients.

WITHDRAWN: Pan-cancer analyses of clinical prognosis, immune infiltration, and immunotherapy efficacy for TRPV family using multi-omics data

“…Fifth, there is also a significant correlation between TRPV in bladder cancer immune infiltration and tumor microenvironment, suggesting that it can predict the effect of immunotherapy. Studies have shown that TRPV affects immune infiltration and prognosis of renal cell carcinoma [ 28 ]. In addition, we also analyzed TRPV mutation and copy number variants in bladder cancer and found that various types of copy number variants were associated with decreased immune cell content.…”

Identification of the common differentially expressed genes and pathogenesis between neuropathic pain and aging

“…We applied the GeneMANIA online database 3 to predict co-DEGs’ PPI network ( Warde-Farley et al, 2010 ). It is an online analysis tool that widely used to demonstrate and evaluate gene interactions ( Jiang et al, 2022 ; Tian et al, 2022 ). Given a query list of genes, GeneMANIA will find more genes like those.…”

A novel TRP channel-related prognostic model of glioma based on transcriptomics and single cell sequencing analysis

“…TRPV3 mainly exists in sensory nerve cells and skin keratinocytes in the human body and senses temperature stimuli by forming a complex with TRPV1(28). Studies have shown that in renal clear cell carcinoma and non-small cell lung cancer, the high expression of TRPV3 is signi cantly correlated with increased tumor grade and poor prognosis, and it affects the accumulation of T cells in various tumor immune microenvironments, which is related to tumor immune in ltration (29,30). Our analysis of singlecell data found that in malignant cells, oligodendrocytes, and endothelial cells, it was expressed in various cells, such as monocytes and macrophages, and may play a complex regulatory role.…”