The Prognostic Value And Tumor Microenvironment Features Of BID Expression In Clear Cell Renal Cell Carcinoma

Objective:Current studies have found that BH3 interaction domain death agonist(BID)is closely related to the occurrence and development of a variety of tumors.However,the interaction between BID and clear cell renal cell carcinoma(ccRCC)has not been clearly reported,and its effect on ccRCC is still unclear.The purpose of this study is to explore the expression of BID in ccRCC,analyze its prognostic value to ccRCC,provide help for risk assessment and survival prediction of patients,and explore its impact on tumor microenvironment(TME),so as to provide theoretical basis for the development of new immunotherapy targets.Methods:The transcriptome information and clinical information of ccRCC and normal kidney tissues were obtained from The Cancer Genome Atlas(TCGA)database,the International Cancer Genome Collaboration(ICGC)database,and the Gene Expression Omnibus(GEO)database,and the data were sorted out by R language.First of all,we performed a differential analysis on the expression levels of BID in ccRCC and normal kidney tissues by R package.Subsequently,ccRCC patients were divided into high-expression group and low-expression group according to the median of expression levels of BID,and the differences in overall survival(OS)and progression free survival(PFS)between the two groups were compared by survival analysis.Then,we evaluated the relationship between the expression levels of BID and the clinical characteristics of patients by correlation analysis.Next,we performed univariate Cox regression analysis and multivariate Cox regression analysis to evaluate whether BID could serve as an independent prognostic factor for predicting the prognosis of ccRCC patients.After that,we built a Cox risk prognosis model in the training cohort,and the validity and stability of the model were further verified in the internal testing cohort,GEO cohort and ICGC cohort.We also constructed a nomogram based on BID and clinical information to further improve the utility of the model in clinic.Furthermore,we validated the results of bioinformatics by transcriptome sequencing and immunohistochemical staining of clinical specimens.Finally,we analyzed the impact of BID on the TME through GSEA enrichment analysis,ssGSEA enrichment analysis,ESTIMATE algorithm,CIBERSORT algorithm,TIDE score and other methods to explore the potential mechanism of BID in the development and progression of ccRCC.Results:Compared with normal renal tissues,BID was highly expressed in ccRCC tissues,which was confirmed by transcriptional sequencing and immunohistochemical staining of clinical specimens.Compared with patients with low expression of BID,patients with high expression of BID had poorer OS and PFS.Clinical correlation analysis showed that the expression levels of BID was higher in male patients,and the high expression of BID predicted worse histological grade and clinical stage,and led to distant metastasis.Univariate and multivariate Cox regression analysis demonstrated that BID was an independent prognostic factor for ccRCC.The prognosis model based on BID can accurately predict the prognosis of patients in different cohorts.In addition,the expression levels of BID is closely related to many immune checkpoint molecules such as PD-1 and CTLA4.Enrichment analysis also showed that BID was significantly enriched in immune-related responses and metabolism-related pathways.The results of correlation analysis showed that the expression levels of BID was closely related to a variety of immune cells.The BID high expression group had high levels of immune cell infiltration and immune activity,and mediated different immune infiltration characteristics of the TME.Conclusion:Highly expressed in ccRCC,BID is a reliable biomarker for predicting the prognosis of patients.It is closely related to the TME,and may be a potential target for immunotherapy for ccRCC patients.