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膀胱癌共刺激因子相关基因预后模型的构建与验证OA北大核心CSTPCD

Construction and verification of prognostic model of bladder cancer costimu-latory molecule-related genes

中文摘要英文摘要

目的:探究膀胱癌预后相关的共刺激因子相关基因,构建并评估基于共刺激因子标志物(CMS)的预后模型.方法:综合TCGA数据库和GEO数据库(GSE31684)下载膀胱癌患者的基因表达矩阵和临床信息,检索文献获得共刺激因子相关基因.利用单因素和多因素Cox分析筛选预后相关基因并构建预后模型,并通过Kaplan-Meier生存分析、受试者工作特征曲线(ROC)等方法在TCGA训练组、TCGA验证数据组和GEO组中独立验证其准确性.结合风险评分和临床特征构建列线图模型,并利用一致性分析和ROC评估其性能.使用反卷积算法(CIBERSORT)分析肿瘤微环境浸润的免疫细胞组成,并进行基因集合富集分析(GSEA)以探究潜在机制.结果:筛选出4个预后相关CMSs:TNFRSF14、CD276、ICOS、TMIGD2,其中3个纳入风险评分构建.多因素Cox分析提示基于CMS的风险评分是膀胱癌患者独立预后因素.一致性分析和ROC结果表明,列线图模型有较好的预后预测准确性.免疫浸润分析显示,高风险组很可能处于免疫抑制状态.GSEA结果提示,高风险组基因富集于细胞外基质(ECM)互作受体、细胞周期等通路中.结论:TNFRSF14、CD276、ICOS可能成为膀胱癌患者潜在预后生物标志物.构建的风险评分和列线图可能有助于膀胱癌患者早期预后评估和个体化治疗的选择.

Objective:To explore genes related to costimulatory molecule related to the prognosis of bladder cancer,and to construct and evaluate prognosis model based on costimulatory molecule-based signature(CMS).Methods:Gene expression matrix and clinical information of bladder cancer patients were downloaded from TCGA database and GEO database(GSE31684),and costimulatory molecule-related genes were retrieved from the literature.The univariate and multivariate Cox analysis were used to screened prognostic-related genes and constructed prognostic model.Forecast accuracy of model was verified in TCGA training group,TCGA validation data group and GEO group by Kaplan-Meier survival analysis and receiver operating characteristic curve(ROC).Considering risk score and clinical characteristics,we constructed a nomogram and evaluated its performance by consistency analysis and ROC.CIBERSORT algorithm was used to analyze immune cell composition of tumor microenvironment infiltration,and gene set enrichment analysis(GSEA)was performed to explore the potential mechanism.Results:Four prognostic-related CMSs were found:TNFRSF14,CD276,ICOS and TMIGD2,of which three were included in the risk score construction.Multivariate Cox regression results showed that the risk score based on CMS was an independent prognostic factor for bladder cancer patients.Consistency analysis and ROC results showed that the nomogram had ideal prognosis prediction accuracy.Immune infiltration analysis showed that the high risk group was likely to be in immunosuppressive state.GSEA results suggested that genes in high risk group were enriched in extracel-lular matrix(ECM)receptors interaction,cell cycle and other pathways.Conclusion:TNFRSF14,CD276 and ICOS may be potential prognostic biomarkers for bladder cancer patients.CMS-based risk score and nomogram could contribute to early prognosis and choice of personalized treatment.

汤鋕城;何朝辉;蔡月桥;廖海琴;卢泽潮;唐福才;卢泽广;张嘉豪;赖永长;阎淑丹

广州医科大学附属第三医院,广州 510000中山大学附属第八医院泌尿外科,深圳 518033广州医科大学第一临床学院,广州 511436广州医科大学第二临床学院,广州 511436广州医科大学第六临床学院,广州 511436

基础医学

共刺激因子膀胱癌预后模型肿瘤免疫微环境

Costimulatory factorBladder cancerPrognostic modelTumor immune microenvironment

《中国免疫学杂志》 2024 (003)

564-571 / 8

国家重点研发计划项目(2018YFA0902801);广东省基础与应用基础研究计划项目(2020A1515010152);深圳市福田区公共卫生研究计划项目(FTWS2020026);广东省大学生创新训练项目(S2021057025).

10.3969/j.issn.1000-484X.2024.03.021

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