膀胱癌预后免疫相关风险模型的构建分析

Construction and analysis of immune-related risk model for prognosis of bladder cancer

目的:通过构建免疫相关风险模型用于评估膀胱癌(bladder cancer,BC)预后,探讨免疫相关基因(immune-related genes,IRGs)在BC临床应用价值。方法:基于TCGA、ImmPort、Cistrom等数据库分别下载BC转录组测序数据(RNA-seq)、IRGs和转录因子(transcription factors,TFs)数据,对差异表达的IRGs行COX回归分析,计算个体免疫-风险评分(RiskScore值)并行Kaplan-Meier生存分析,差异表达的IRGs与TFs进行网络调控分析,结合RiskScore值分析22种免疫浸润细胞在BC的差异表达。结果:共有22个IRGs与BC患者的临床预后显著相关,行KEGG分析显示细胞因子-细胞因子受体相互作用是IRGs最常见作用途径;以MMP9、PAEP、ADIPOQ、AHNAK、OAS1、RAC3、IL34、PDGFD、SH3BP2为基础构建的免疫-风险模型,行Kaplan-Meier生存分析提示低风险组生存预后明显好于高风险组(P<0.001);差异表达的16个TFs及7个IRGs纳入性网络调控分析,ENDRA、IGF1、RAC3作为调控网络的核心;基于IRGs的RiskScore值反映了多种免疫细胞浸润相关情况。结论:我们所构建的免疫-风险模型可用于预测BC患者生存预后,进一步研究发现BC中多种免疫细胞浸润情况,这可能有助于扩大免疫治疗的应用范围。

Objective:To evaluate the prognosis of bladder cancer(BC) by constructing an immune-related risk model,and to explore the clinical application value of immune-related genes(IRGs) in BC.Methods:Respectively based on TCGA,ImmPort,Cistrom database,BC transcriptome sequencing data-seq,IRGs and Transcription factor(TFs) data were download.COX regression analysed differentially expressed IRGs.Risk score was calculated and Kaplan-Meier survival analysis was made.Differential expression of IRGs and TFs was analysed network regulation analysis.The differential expression of 22 immunoinfiltrating cells in BC was analyzed with Riskscore.Results:A total of 22 IRGs were significantly associated with the clinical outcome of BC patients.Functional enrichment analysis revealed that these genes were actively involved in acytokine-cytokine receptor interaction KEGG pathway.The immuno-risk model based on MMP9,PAEP,ADIPOQ,AHNAK,OAS1,RAC3,IL34,PDGFD,SH3 BP2,Kaplan-Meier survival analysis showed that the survival prognosis of the low-risk group was significantly better than that of the high-risk group(P<0.001).The network regulation analysis showed of 16 TFs and 7 IRGs differentially expressed ENDRA,IGF1,RAC3 as the core of the regulatory network.Riskscore value based on IRGs reflect a variety of immune cell infiltration related conditions.Conclusion:Our immune-risk model can be used to predict survival prognosis in patients with BC,and further studies have found multiple immune cell infiltration in BC,which may help expand the scope of application of immunotherapy.