The Expression And Significance Of TRPV4 In Ovarian Cancer Were Analyzed Based On Bioinformatics

Background:Ovarian cancer(OV)is one of the three deadliest gynecologic malignancies,and the main treatment currently is surgery combined with platinum-based chemotherapy.The 5-year survival rate of ovarian cancer is less than 40% due to the difficulty of early diagnosis,rapid metastasis and terminal drug resistance.The specific pathogenesis of ovarian cancer is not fully clarified,and the high recurrence rates,high metastasis rates and chemoresistance remain a dilemma for clinical treatment.Therefore,it is very urgent to explore more sensitive biomarkers and effective therapeutic targets for ovarian cancer.TRPV4,a member of TRP family,is a widely expressed multi-modal activated ion channel.It has been reported that TRPV4 is highly expressed in a variety of tumor tissues,such as gastric cancer,breast cancer,and colon cancer.Studies on the role and mechanism of TRPV4 in ovarian cancer have not been reported.This study aimed to confirm the expression and prognostic value of TRPV4 and its correlation with immune cell infiltration in ovarian cancer.Methods:1.UCSC Xena Shiny was used to predict the difference of m RNA expression of TRPV4 in OV.2.Univariate and multivariate Cox regression analysis was used to predict the clinical prognostic value of TRPV4 in patients with TCGA-OV,and a clinical predictive model was constructed.3.GSEA,GO,and KEGG enrichment analysis were used to predict the way and mechanism by which TRPV4 affects the occurrence and progression of OV.4.CIBERSORT was used to explore the regulatory role of TRPV4 in the immune microenvironment of OV and the correlation of TRPV4 with immune checkpoint molecules was analyzed.Results:1.Based on the results of UCSC Xena Shiny and GEPIA database analysis,the TRPV4 m RNA expression in ovarian cancer tissues was significantly higher than that in normal ovarian tissues.94.5% area under the ROC curve for the diagnosis of TCGA-OV by TRPV4.2.According to the median of TRPV4 m RNA,patients were divided into high and low groups,K-M curve results showed that high TRPV4 expression was closely correlated with low OS and DSS in TCGA-OV patients.The results of univariate and multivariate COX regression analysis suggested that TRPV4 could be an independent prognostic factor for ovarian cancer.3.TRPV4 was involved in EMT,ECM receptor interaction,cytokine-cytokine receptor interaction,inflammatory response,and was closely related to the activation of KRAS signaling up,IL2/STAT5 Signaling,IL6/JAK/STAT3 signaling,WNT＿βcatenin signaling,calcium signaling pathway,Hedgehog signaling pathway,Pathways In Cancer.4.CIBERSORT analysis results showed that the expression level of TRPV4 was correlated with the immune infiltration of ovarian cancer,which was positively correlated with the infiltration of T cells regulatory(Tregs),and negatively correlated with B cells memory,Macrophages M1,Dendritic cells activated,T cells follicular helper,T cells gamma delta.In addition,immune checkpoint genes correlation analysis showed that TRPV4 was significantly and positively correlated with most immune checkpoint molecules(PD-L1,HAVCR2,PD1,PD-L2).Conclusions:1.Compared with normal ovarian tissue,TRPV4 is highly expressed in ovarian cancer.2.High TRPV4 might serve as an independent risk factor for poor prognosis in patients with TCGA-OV.3.TRPV4 may influence the malignant behavior of OV cells through regulating the tumour immune microenvironment.