Genetic Landscape And Clinical Characteristics And Prognosis Of BAP1 Mutation In Renal Clear Cell Carcinoma

Objective: To establish a gene mutation profile of cc RCC in Xinjiang using next-generation sequencing targeted sequencing,to clarify whether there are differences in the gene mutation profiles of cc RCC patients in Xinjiang and western populations,to reveal the characteristics of BAP1 gene mutations in cc RCC patients in Xinjiang,to reveal the effects of BAP1 mutations on the clinical features,pathological staging and histological grading of renal clear cell carcinoma patients,and to clarify BAP1 mutation on the survival and prognosis of cc RCC patients.Methods: The gene mutation spectrum of 269 patients with cc RCC in our hospital was compared with that of 512 patients with cc RCC in the TCGA by ultra-deep targeted sequencing,and the patients were divided into BAP1 mutation group and BAP1 non-mutation group according to the key gene BAP1 mutation,,and the signaling pathways and GO enrichment analysis of cc RCC mutated genes were understood by bioinformatics.The relationship between BAP1 mutation and clinical characteristics,progression-free survival(PFS),and overall survival(OS)was analyzed using Kaplan-Meier survival analysis,and multivariate Cox proportional risk regression models were used to further determine A multivariate Cox proportional risk regression model was used to further determine the independent prognostic influences on PFS and OS in cc RCC patients.The c Bioportal database was used to analyse the TCGA of cc RCC patients with BAP1 mutations in relation to pathological stage,histological grading,progression-free survival,disease-free survival,disease-specific survival,and overall survival by plotting K-M survival curves.Results:(1)Analysis of the correlation between clinical characteristics and BAP1 mutation in our patients with renal cc RCC suggested that: first symptoms(P=0.002),history of hypertension(P=0.011),WHO/ISUP grading(P<0.001),primary stage(P<0.001),M stage(P<0.001),and earliest metastatic site(P=0.003)on cc RCC BAP1 mutation were significantly correlated.(2)Age(P=0.010),gender(P=0.049),BMI(P<0.001),history of coronary heart disease(P=0.048),stage(P=0.023),T-stage(P=0.002),distant metastasis(P=0.012),treatment modality(P<0.001),and BAP1 mutation(P=0.012)had a significant effect on progression-free survival of patients with cc RCC,and primary stage,T stage,N stage,M stage,and distant metastasis of the tumor were independent risk factors for the prognosis of patients with renal clear cell carcinoma(3)Univariate analysis of overall survival yielded results for age(P<0.001),history of hypertension(P=0.011),history of diabetes(P=0.038),history of coronary heart disease(P=0.001),WHO/ISUP classification(P<0.001),stage(P<0.001),T-stage(P=0.001),N-stage(P=0.001),M-stage(P < 0.001),earliest site of metastasis(P < 0.001),treatment modality(P=0.026),and BAP1 mutation(P=0.043)on renal cc RCC patients had a significant impact on overall survival.Age,T-stage,N-stage,and earliest metastatic site of tumour were independent risk factors for overall survival.(4)Our patients with cc RCC were mapped by ultra-deep targeted sequencing,and the high frequency mutated genes included VHL(83%),PBRM1(38%),SETD2(14%),BAP1(14%),and KDM5C(8%).(5)The top 5high-frequency mutated genes in cc RCC patients in the TCGA database were VHL(47%),PBRM1(40%),TTN(19%),SETD2(13%),and BAP1(11%),and missense mutation occurred 16,422 times among the gene mutation types,accounting for the most,at 52.85%The number of missense mutations in the genes was 16,422,accounting for 52.85%,similar to that in Xinjiang.(6)Bioinformatics analysis of GO and KEGG can be obtained that cc RCC differential genes mainly affect focal cell adhesion,transmembrane transport and so on to participate in the process of renal clear cell carcinogenesis.(7)Mutations in the key gene BAP1 could affect AJCC staging,T/N/M staging,and WHO/ISUP grading,which were consistent with the population in Xinjiang(P<0.05),while shortening patients’ DFS,PFS,DSS,and OS.Conclusion:(1)the frequency of BAP1 mutations was slightly higher in the population of the Xinjiang region of renal clear cells than in the Western population,with little difference in the top five overall mutated genes;(2)BAP1 had an effect on progression-free survival and overall survival of patients with renal clear cell carcinoma.