Analysis of KDM6A mutation,prognosis and immune microenvironment in bladder urothelial carcinoma
Objective To identify key gene mutations and explore their mechanisms in bladder urotheli-al carcinoma(BLCA)through bioinformatics analysis combined with clinical sample testing.Methods Gene mutation data,transcriptome data,and clinical data for all BLCA cases were downloaded from the TCGA data-base(406 tumor tissues and 19 adjacent non-cancer tissues)and GTEx database(21 adjacent non-cancer tis-sues).A total of 32 clinical samples from BLCA surgeries were collected,and gene expression was measured using real-time quantitative polymerase chain reaction(PCR).Results Mutations were found in 91.42％of the patients,with missense mutations,single nucleotide variants,and C＞T transitions being the predominant types.The top five mutated genes were TP53(47％),TTN(45％),KMT2D(29％),MUC16(28％),and KDM6A(26％).In both TCGA and clinical samples,the expression levels of mutant KDM6A were significant-ly higher than those of the wild type(P=0.008,0.007).The patients with wild-type KDM6A had a longer o-verall survival(OS)and progression-free survival(PFS)than those with the mutation(P=0.028,0.035).Fur-ther studies revealed that the expression of KDM6A was significantly positively correlated with the levels of CD8+T cells(r=0.22,P=0.039),macrophages(r=0.31,P=0.032),and endothelial cells(r=0.26,P=0.002).Conclusion Mutations in KDM6A are closely associated with prognosis and the immune microenvi-ronment in BLCA,suggesting that KDM6A mutations may serve as potential therapeutic targets for BLCA.
万方数据
维普
