Tumor Antigen And Immune Subtype Analysis For Bladder Cancer MRNA Vaccine Development

Object iveBladder cancer is a common malignant tumor in the urinary system,and its morbidity and fatality rate are increasing year by year.Research hotspots.Increasing evidence shows that tumor-specific antigens,immune checkpoint molecules and tumor microenvironment are closely related to the occurrence and development of cancer.Mutated antigens can activate the immune system to a certain extent to overcome the immunosuppressive state caused by tumors,enhance the activation of immune function,and achieve anti-tumor therapy.This study explores the preliminary development of cancer therapeutic vaccines by identifying mutated genes and prognosis-related antigens in bladder tumors.In addition,molecular typing of bladder cancer related to immune signatures was identified,and immune-related signatures of different subtypes of tumors were analyzed based on the status of the immune microenvironment,in order to distinguish patients in heterogeneous cohorts and select appropriate treatment groups.Methods Gene expression profiles and corresponding follow-up data were obtained from the TCGA and GEO databases,and the Imm Port database extracted a complete list of immune-related genes.Visualization and analysis of mutation data by c Biopotal,based on the correlation of immune cells with tumor mutation prognostic antigens in TIMER.Potential tumor antigens were gradually narrowed down by amplification,mutation,prognosis,and immune cell infiltration correlations,and the expression of the screened antigens was validated by quantitative real-time PCR(q RT-PCR).GEPIA conducts survival analysis of mutated prognostic genes,uses unsupervised consistent clustering to analyze immune subtypes based on immune expression,compares immune microenvironments between subtypes,and uses manifold learning algorithms to construct immune landscapes to display individual bladder cancer immunity sign.WGCNA was correlated with immunophenotype by expression cluster analysis.Identify key modules,as well as feature root gene comparisons across different subtypes across different modules,pathway enrichment analysis,and compare modules for PCA correlations.Results According to the analysis,three prognostic associations could be potential tumor-specific antigens(CYTH3,OSBPL6 and EHBP1)for m RNA vaccine treatment,and q RT-PCR showed significantly high expression of both antigens in bladder cancer cell lines.Moreover,bladder cancer patients were identified into two immune-related subtypes,IS1 and IS2,IS2 patients had higher survival than IS1 patients,and analyzed the immune microenvironment between different subtypes,IS1 patients showed thermal immune status and IS2 patients showed cold immune status.According to the comparison of different immunotyping immunotherapy indexes,there were significant differences in the expression of both immune checkpoints and immunogenic cell death regulators.The immune map revealed the immune status of individual patients,especially in IS2 patients.WGCNA identifies 14 immune-gene-related modules.IS1 characteristic root genes were significantly higher than IS2,red module was associated with green module and PCA,and IS1 in red module had poor prognosis.Conclusion This study preliminarily characterized CYTH3 and OSBPL6 tumor antigens as potential tumor-specific antigens for developing anti-bladder m RNA vaccine,and WGCNA also provides potential targets for targeted treatment of bladder cancer.According to immune correlation analysis,I S type 1 patients are more suitable for immunotherapeutic tumor vaccine.Figure 19 reference 45...