To Explore The Expression And Clinical Significance Of FOLR 1 Gene In Renal Clear Cell Carcinoma Based On Multiple Databases

Background and ObjectiveRenal cell carcinoma(Renal Cell Carcinoma,RCC),also known as renal adenocarcinoma,kidney cancer,is a common urinary system tumor,its incidence of urinary system tumors is in the third(after prostate cancer and bladder cancer),but it is the highest lethal rate of urinary system malignant tumor.The histopathology of RCC is diverse,among which renal clear cell carcinoma(Clear Cell Renal Cell Carcinoma,cc RCC)is the most common.Patients with early cc RCC have no obvious positive signs,and about 20%-30% of patients have distant metastasis at treatment,which often leads to poor prognosis.As tumor markers have been found and applied to clinical,makes many tumor disease early diagnosis more accurate,prognostic level increased significantly,so looking for effective cc RCC tumor markers,and study its regulation mechanism and involves the signaling pathway,for the early diagnosis and treatment of cc RCC,prognosis evaluation to provide strong evidence is particularly important.Folate-binding receptor 1(Folate Receptor 1,FOLR 1),located on human chromosome 11q13.3-14.1,mainly encodes a glycosylated phosphatidylinositol protein with a high affinity for folate and its derivatives.Studies have shown that FOLR 1 is highly expressed in ovarian cancer,nasopharyngeal carcinoma,breast cancer and other tumors,which is an independent poor prognostic indicator,while the expression level and clinical significance in renal clear cell carcinoma have not been clarified.This paper mainly discusses the expression level and clinical significance of FOLR 1 in cc RCC patients,and provides new ideas for the diagnosis,treatment and prognosis of cc RCC.MethodFirstly,RNA-Seq expression data and clinical information of patients were downloaded from Cancer Genome Atlas(The Cancer Genome Atlas,TCGA)database.Using bioinformatics method,the above data were collated by R language and Excel software,and statistical differences of gene expression and clinical information were analyzed by Prism and SPSS software.The GSE40435 package from the Gene Expression comprehensive database(Gene Expression Omnibus,GEO)was downloaded to verify the results of the TCGA database using the same method.Data downloaded from the TCGA database,the Kaplan-Meier survival curve analysis was used to understand the prognostic impact of FOLR 1 expression level on cc RCC patients,and univariate and multivariate Cox regression analysis was used to understand the relationship between FOLR 1 gene and clinicopathological information in cc RCC patients.Immune cell infiltration in cc RCC tissues was obtained by Cibersort method.GO and KEGG enrichment analysis of FOLR 1 using GSEA 4.3.2 software to explore the potential functions and related signaling pathways of FOLR 1 in cc RCC.The proteins with interactions with the FOLR 1 gene were predicted using the STRING database.ResultBioinformatics methods showed that the expression level of FOLR 1 in cc RCC tumor tissues was significantly lower than that of adjacent tissues(P <0.0001),and the overall survival rate(OS)of patients with high FOLR 1 gene expression was significantly higher than that of the low expression group(HR:0.952;95%CI:0.932-0.995;P = 0.017).According to Cox regression analysis,the expression level of FOLR 1 gene was closely related to patient age,clinical stage,T stage,T stage,N stage,M stage,pathological grade,and chemoradiotherapy selection measures,but showed no significant statistical difference with sex.The Cibersort method learned that FOLR 1 had the greatest correlation with NK activated cells,monocytes,and CD4 memory cells in cc RCC tissues.Through GO function enrichment analysis,FOLR 1 may be related to fatty acid oxidation,protein binding,branched chain amino acids,leucine catabolism process,and mitochondrial function;and KEGG pathway enrichment analysis showed that FOLR 1 may participate in P53 signaling pathway,G2 / M signaling pathway,antidiuretic hormone signaling pathway,proximal renal tubular reabsorption bicarbonate signaling pathway,citric acid cycle,cell cycle signaling pathway,etc.Ten proteins interacting with the FOLR 1 gene were predicted as TYRO 3,FGF3,SCFD1,STX 17,AXL,PCBP1,LRP 2,GPT,SLC19A1,and SLC46A1.Meanwhile,the GO function enrichment analysis of the above proteins showed that the function of FOLR 1 interacting protein was mainly related to the entry of folate into cells,plasma membrane and folate binding.Conclusion1.FOLR 1 expression was significantly lower in cc RCC tissues than in adjacent tissues,And showed a negative correlation with patient Age,tumor size T,lymph node status N,distant metastasis M,tumor Grade,clinical Stage;2.FOLR 1 is associated with the prognosis of cc RCC patients,And for its protective factor,FOLR 1can be used as a potential tumor marker of cc RCC;3.FOLR 1 mainly affects NK activated cells,monocytes,CD4 memory cells in cc RCC tissues;4.FOLR 1 may cause oxidation with fatty acids,PB,Mitochondrial organization and function,Branches chain amino acids,leucine,valine metabolic process related;Participate in P53 signaling pathway,G2 / M signaling pathway,vasopressin-regulated water reabsorption,proximal renal tubular reabsorption of bicarbonate,citric acid cycle,and cell cycle;5.There are 10 proteins interacting with FOLR 1,And TYRO 3,FGF3,SCFD1,STX 17,AXL,PCBP1,LRP 2,GPT,SLC19A1,and SLC46A1,respectively,And is associated with folic acid entry into cells,the plasma membrane,and folic acid binding.