基于DNA损伤修复基因的膀胱癌预后风险模型构建及其在免疫治疗效果预测中的应用  

Construction of a bladder cancer prognostic risk model based on DNA damage repair and its application in predicting the effectiveness of immunotherapy

作　　者：罗鸿程 张嘉豪 何朝辉[1] LUO Hong-cheng;ZHANG Jia-hao;HE Zhao-hui(The Eighth Affiliated Hospital,Sun Yat-sen University,Shenzhen,Guangdong 518033,China)

机构地区：[1]中山大学附属第八医院泌尿外科,广东深圳518033

出　　处：《岭南现代临床外科》2024年第1期26-36,共11页Lingnan Modern Clinics in Surgery

基　　金：国家重点研发计划(2018YFA0902801)。

摘　　要：目的本研究旨在探索构建一个基于DNA损伤修复相关基因(DDRGs)的预测膀胱癌患者生存预后及免疫治疗效果的风险模型。方法首先,从TCGA⁃BLCA数据集下载的RNA序列及临床信息,通过单变量Cox、最小绝对收缩与选择算法(LASSO)及多变量Cox分析,筛选出与DNA损伤修复相关的基因(DDRGs),构建预后风险模型;利用Kaplan⁃Meier生存曲线评估生存差异,通过接收者操作特征(ROC)曲线验证模型性能,并结合临床特征构建列线图进行验证。最后,对临床特征进行了分层分析,并进一步通过基因集富集分析(GSEA)、评估免疫状态和免疫检查点抑制剂(ICIs)的治疗效果。结果通过构建11个DNA损伤修复相关基因的风险模型,显示高风险得分的膀胱癌患者生存率明显低于低风险得分患者。免疫状态的分析揭示了高风险与低风险组之间存在显著差异,且低风险组患者对免疫检查点抑制剂的治疗效果更佳。结论基于DNA损伤修复构建的预后风险模型能有效预测膀胱癌患者的生存预后及其对免疫检查点抑制剂治疗的响应性。Objective This study aims to explore the construction of a risk model based on DNA Damage Repair Genes(DDRGs)that can accurately predict the survival prognosis and immunotherapy outcomes of bladder cancer patients.Methods Initially,RNA sequences and clinical information down⁃loaded from the TCGA⁃BLCA dataset were analyzed through univariate Cox,Least Absolute Shrinkage and Selection Operator(LASSO),and multivariate Cox analyses to identify DNA Damage Repair Genes(DDRGs)and construct a prognostic risk model.Subsequently,the Kaplan⁃Meier survival curve was utilized to assess survival differences,the Receiver Operating Characteristic(ROC)curve to validate model performance,and nomograms were constructed incorporating clinical features for further validation.Lastly,clinical features were subjected to stratified analysis,and the treatment effects of immune status and Immune Checkpoint Inhibitors(ICIs)were further evaluated through Gene Set Enrichment Analysis(GSEA).Results The risk model constructed with 11 DNA damage repair⁃related genes showed that bladder cancer patients with high⁃risk scores had significantly lower survival rates than those with low⁃risk scores.Conclusion The prognostic risk model constructed based on DNA damage repair in this study can effectively predict the survival prognosis of bladder cancer patients and their responsiveness to treatment with Immune Checkpoint Inhibitors(ICIs).

关 键 词：膀胱癌 DNA损伤修复 预后模型 免疫治疗 

分 类 号：R737.14[医药卫生—肿瘤]