Exploring The Pathological Mechanism Of Bladder Cancer Based On Tumor Mutation Burden Analysis

Objective Immunotherapy plays an important role in bladder cancer(BC).Tumor mutation burden(TMB)is closely related to immune microenvironment.To explore the pathological mechanism of bladder cancer based on TMB analysis may clarify the immune mechanism of bladder cancer and provide a new biomarker for clinicians.Methods Data for 412 BC samples were downloaded from the TCGA database.And the TMB was calculated.Then BC samples were divided into high-TMB group and low-TMB group.The correlation between TMB and clinical data was analyzed,and survival curves were plotted.The differential expressed genes(DEGs)of the two TMB groups were found using the lima program package.Then,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed.The function of the DEGs was analyzed using the clusterprofiler software package.GEPIA was used to investigate the relationship between DEGs and the overall survival of patients with bladder cancer.Finally,the relationship between TMB and immune microenvironment in bladder cancer was established,and immune cells changes in bladder cancer were found.Results(1)The most common mutations in the BC are missense mutations.SNPs accounts for the majority of the mutation type.The C>T transition in the SNV classification accounts for the largest part,followed by the C>G transition.Mutant TP53 and mutant FGFR3 are mutually exclusive,while mutant TP53 and mutant RB1are coexist.Mutant TTN coexists significantly with mutant ERBB2,OBSCN,FAT4,ATM,MACF1,MUC16.(2)The survival rate of the group with high-TMB was significantly higher than that of the group with low-TMB.The results showed that TMB was associated with gender.(3)69 DEGs were identified.Among them,46genes were highly expressed in the low-TMB group,while 23 genes were highly expressed in the high-TMB group.23 genes were highly expressed in the high TMB group and 46 genes were poorly expressed.(4)The GO results were enriched into 19terms,KEGG pathway enrichment indicated that 4 DEGs were involved in the"Renin-angiotensin system"pathway.(5)17 genes were significantly associated with the overall survival with BC.The expression of these genes in BC is lower than in normal tissue.(6)Compared with the low-TMB group,the samples with high-TMB had higher levels of T cells CD8~+,T cells CD4~+memory activated and NK cells resting,while Mast cells resting was lower.Conclusion 17 genes screened in this work which are related to prognosis and hoped to be used as targets for bladder cancer treatment.Immune cells related to TMB in BC,which is expected to promote the clinical application of existing immunotherapy programs in this disease,were also analyzed.