Bioinformatics Analysis Of VSIG4 Expression In The Renal Clear Cell Carcinoma And Its Correlation With Tumor Infiltrating Immune Cells

Background:Clear cell renal cell carcinoma(ccRCC)is the most common type of renal cell carcinoma,accounting for about 80%of all renal cell carcinomas.At present,surgical resection,radiotherapy and chemotherapy are the main treatment methods for ccRCC,which are effective for patients with early ccRCC.However,ccRCC often progresses to the advanced stage when found,resulting in poor prognosis.Several studies have shown that changes in the expression of specific genes are highly associated with the development and progression of ccRCC.Therefore,mining the potential biomarkers of ccRCC is of great significance to improve patient prognosis and is expected to provide new targets for the treatment of ccRCC.V-set and immunoglobulin domain containing 4(VSIG4)is highly expressed in a variety of cancers such as liver cancer,lung cancer,breast cancer and ovarian cancer.VSIG4 can promote tumor cell proliferation,invasion,and migration by regulating the tumor microenvironment(TME).However,there are few studies on VSIG4 expression and function in ccRCC,and no studies on VSIG4regulation on M2 macrophage infiltration have been reported.Therefore,this article will analyze the expression of VSIG4 in ccRCC and its effect on prognosis,as well as its correlation with the immune microenvironment,in order to provide theoretical basis for exploring potential biomarkers of ccRCC.Objective:1、To analyze VSIG4 expression in ccRCC and its relationship to prognosis;2、To explore the correlation between VSIG4 and M2 macrophage infiltration in ccRCC microenvironment.Methods:1、The ccRCC transcriptome and clinical data were downloaded from the Cancer Genome Atlas(TCGA)database.ESTIMATE and CIBERSORT algorithms were used to determine the levels of immune/stromal components and the proportion of tumor-infiltrating immune cells(TIICs)in 611 ccRCC samples.2、Differentially expressed genes(DEGs)were screened by multiple univariate Cox regression analysis and protein-protein interaction(PPI)network.Through this process,V-set and immunoglobulin domain containing 4(VSIG4)was identified as potential predictors.3、Wilcoxon rank-sum test was used to analyze VSIG4 m RNA expression in ccRCC and normal renal tissues.The correlation between VSIG4 expression and clinicopathological parameters was analyzed by Wilcoxon rank-sum or Kruskal-Wallis rank-sum test.Kaplan-Meier was used to analyze the correlation between VSIG4 expression and patient prognosis.Gene set enrichment analysis(GSEA)was used to explore the signaling pathway of VSIG4 in ccRCC.The correlation between VSIG4 level and tumor infiltrating immune cells was analyzed via CIBERSORT in R software.4、Western blotting was used to detect VSIG4 protein level in human renal epithelial cell line,293T,and human renal carcinoma cell line,ACHN,A498and OS-RC-2.Immunohistochemistry was used to identify VSIG4 expression in59 ccRCC and paired adjacent tissues.Results:1、Analysis of TCGA data,immunohistochemistry,and Western blot results all showed that VSIG4 expression levels in ccRCC were higher than in normal tissues and were associated with poor patient outcomes.2、The infiltration of M2 macrophages and Foxp3~+Treg cells in the VSIG4 high expression group was significantly increased.Conclusion:VSIG4 is highly expressed in ccRCC and is associated with poor patient outcomes.VSIG4 may be related to the polarization of M2 macrophages in the tumor environment.