【摘要】 目的:通过生物信息学的方法分析并确定膀胱癌患者的关键焦亡相关基因(PRGs)表达谱,并阐明其潜在功能。方法:从癌症基因组图谱(TCGA)数据库中下载了对应膀胱样本的mRNA表达谱和临床数据,进行功能富集分析,包括基因本体论分析(GO)和京都基因与基因组百科全书的分析(KEGG)。构建评估预后的基因模型,计算风险评分,分高、低风险组评估膀胱癌的预后。评估PRGs与肿瘤免疫浸润的相关性,并构建基于它们的共表达和预测目标的竞争性内源性RNA(ceRNA)调控轴。结果:我们选择了33个PRGs,功能富集分析显示,它们主要参与细胞因子产生、炎症小体复合物、凋亡过程和NOD样受体信号通路的正调控。我们用LASSO Cox回归分析筛选6个基因(CASP9、PRKACA、CASP6、TNF、AIM2、GSDMB)构建PRGs模型,KM曲线提示高风险评分的膀胱癌患者的总生存时间概率低于低风险评分患者,差异有统计学意义(P<0.001),列线图表明该模型对预后预测较准确。AIM2、CASP6与免疫细胞浸润显著相关(P<0.05)。通过构建ceRNA网络,确定了膀胱癌中的CASP6/hsa-let-7c-5p/MIR29B2CHG调控轴。结论:预后相关的PRGs与膀胱癌患者免疫细胞浸润显著相关。膀胱癌的CeRNA调控轴尚需进一步验证。更多还原

【Abstract】 Objective:To identify key pyroptosis-related genes(PRGs)in patients with bladder cancer(BLCA)by performing bioinformatics analysis and to clarify their potential value.Methods:We downloaded the mRNA expression profiles and clinical data corresponding to bladder samples from The Cancer Genome Atlas(TCGA)database.Next,we performed functional enrichment analyses,including both Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)and analyses,to evaluate the mechanism underlying the signature.In addition,a comprehensive bioinformatics analysis was performed,and we constructed a prognostic gene model.The correlations between PRGs and tumor immune infiltration and microsatellite instability were evaluated.Moreover,we constructed a competing endogenous RNA(ceRNA)regulatory axis based on their coexpression and predicted targets.Results:We selected 33 PRGs,and functional enrichment analyses revealed these PRGs are mainly involved in the positive regulation of cytokine production,inflammasome complexes,apoptotic processes,and NOD-like receptor signaling pathways.A prognostic PRG model constructed using the 6 prognostic genes predicted the overall survival(OS)of BLCA patients with medium-to-high accuracy.The genetic mutation landscape of the PRGs in BLCA was also summarized.A significant correlation was observed between prognostic PRGs(AIM2 and CASP6)and immune cell infiltration and microsatellite instability.A ceRNA network was constructed and identified the CASP6/hsa-let-7c-5p/MIR29B2CHG regulatory axis in BLCA.Conclusion:The prognostic PRGs were significantly correlated with immune cell infiltration and microsatellite instability in BLCA patients.A CASP6/hsa-let-7c-5p/MIR29B2CHG regulatory axis for the BLCA are needed to verify.更多还原