Screening Immune-related Prognostic Biomarkers Of Clear Cell Renal Cell Carcinoma Based On Bioinformatics

Objective:Renal cancer is one of the top ten most common malignancy in the world,of which75-80%of patients are clear cell renal cell carcinoma(ccRCC).Patients with ccRCC have the highest mortality and metastasis rates.And most patients with ccRCC are not sensitive to chemotherapy and radiotherapy.Tumor immunotherapy has high efficacy and safety.Combined with traditional treatment,it can significantly improve the quality of patients'life,but not all patients can benefit from it.There are problems such as low response rate and drug resistance,so it is necessary to develop new and effective immunotherapy targets as drug targets for tumor immunotherapy or combination therapy.In this study,bioinformatics was used to discover the genes related to diagnosis and prognosis of ccRCC and immunotherapy,to explore the expression of LILRB3 in ccRCC and the relationship with patient prognosis,to evaluate its value as a biomarker for diagnosis and survival prediction,and to provide preliminary reference for diagnosis and treatment of ccRCC.Methods:The TCGA database and immune gene sets were used to screen genes with high expression in ccRCC and related to immunity.In this study,there were 531 renal clear cell carcinoma tissues and 72 normal tissues.The screening conditions for differential genes were FC>2,P<0.01.Survival analysis and ROC curve analysis were used to obtain genes with prognostic value and diagnostic value for ccRCC.Through Cox single factor and multiple factor regression analysis,lilrb3 is an independent risk factor.Finally,LILRB3 was selected as the target gene.The screening condition was P<0.05.The expression level and prognostic value of LILRB3 were analyzed by TCGA database.The genes co-expressed with LILRB3 were screened by cBioPortal for Cancer Genomics,and the functional annotation and pathway enrichment of LILRB3co-expressed genes were performed by DAVID.The screening condition was Pearson correlation analysis|r|?0.5,The TIMER database was used to analyze the effect of LILRB3 on immune infiltration in tumor microenvironment.Analysis of the relationship between LILRB3 and important immune checkpoints Results:1.We obtained 3719 up regulated genes in ccRCC from TCGA database.2.We obtained 355 genes from the intersection of 3719 up regulated genes in ccRCC and immune gene sets.3.The above 355 genes were analyzed for survival analysis and 100 genes were obtained with statistical significance.4.Using ROC curve to analyze the above 100 genes,the top ten genes with the most diagnostic efficacy are TREM2,CD68,GNLY,L2RB,ISG20,FCGR1A,CCL5,GZMH,LILRB3,and ZAP70.5.Through Cox risk regression model,LILRB3 was an independent risk factor.Therefore,lilrb3 was selected as the target gene of this study,we took its expression level back to TCGA database and GEO database and demonstrated that the expression level of LILRB3 in ccRCC was higher than that in normal tissues.6.Survival analysis and Cox risk regression model analysis showed that patients with high expression of LILRB3 had a lower survival rate and poorer prognosis.7.GO and KEGG pathway enrichment analyses showed that LILRB3 is involved in biological processes like immune response,inflammatory response,T cell co-stimulation,signal transduction and signaling pathways like T cell receptor signaling pathway,chemokine signaling pathways,antigen processing and presentation pathways.8.The TIMER database shows that the overexpression of LILRB3 is related to the infiltration of dendritic cells,macrophages,B cells,CD8~+T cells,CD4~+T cells,neutrophils,and tumor purity in ccRCC.LILRB3 plays an important role in the immune infiltration of the ccRCC microenvironment.9.Correlation analysis showed that LILRB3 was positively correlated with immune checkpoints PD-1,PD-L1,CTLA4,LAG3,IDO1,TIM3,TIGIT and VISTA.Conclusions:In this paper,we used bioinformatics methods to analyze and process various data.LILRB3 is selected as the target gene.LILRB3 is overexpressed in ccRCC.Patients with high expression of LILRB3 have poor prognosis.LILRB3 plays an important role in immune infiltration of clear cell renal cell carcinoma microenvironment.These results indicate that LILRB3 can be used as a potential new prognostic and therapeutic target for clear cell renal cell carcinoma.