TDERS,an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer:a multicohort study  

作　　者：Aimin Jiang Ying Liu Ziwei He Wenqiang Liu Qiwei Yang Yu Fang Baohua Zhu Xiaofeng Wu Huamao Ye Bicheng Ye Shunxiang Gao Le Qu Wenhao Xu Peng Luo Linhui Wang 

机构地区：[1]Department of Urology,Changhai Hospital,Naval Medical University(Second Military Medical University),Shanghai,China [2]Department of Urology,Shanghai East Hospital,Tongji University School of Medicine,Shanghai,China [3]Department of Urology,the Third Affiliated Hospital of Naval Military Medical University(Eastern Hepatobiliary Surgery Hospital),Shanghai,China [4]School of Clinical Medicine,Medical College of Yangzhou Polytechnic College,Yangzhou,China [5]Eye Institute and Department of Ophthalmology,Eye&ENT Hospital,Fudan University,Shanghai,China [6]Department of Urology,Affiliated Jinling Hospital,Medical School of Nanjing University,Nanjing,China [7]Department of Urology,Fudan University Shanghai Cancer Center,State Key Laboratory of Genetic Engineering,Collaborative Innovation Center for Genetics and Development,School of Life Sciences,Institute of Biomedical Sciences,and Human Phenome Institute,Fudan University,Shanghai,China [8]Department of Oncology,Zhujiang Hospital,Southern Medical University,Guangzhou,China

出　　处：《Journal of the National Cancer Center》2024年第4期382-394,共13页癌症科学进展（英文）

基　　金：funded by grants from the National Natural Science Foundation of China(grant numbers:82002664,81872074,81772740,82173345 and 82373154);the Hanghai Jiading District Health Commission Scientific Research Project Youth Fund(grant num-ber:2020-QN-02);the Meng Chao Talent Training Plan-Youth Re-search Talent Training Program of Eastern Hepatobiliary Surgery Hos-pital and the Foundation for Distinguished Youths of Jiangsu Province(grant number:BK20200006).

摘　　要：Background:Tumor-derived exosomes are involved in tumor progression and immune invasion and might func-tion as promising noninvasive approaches for clinical management.However,there are few reports on exosom-based markers for predicting the progression and adjuvant therapy response rate among patients with clear cell renal cell carcinoma(ccRCC).Methods:The signatures differentially expressed in exosomes from tumor and normal tissues from ccRCC pa-tients were correspondingly deregulated in ccRCC tissues.We adopted a two-step strategy,including Lasso and bootstrapping,to construct a novel risk stratification system termed the TDERS(Tumor-Derived Exosome-Related Risk Score).During the testing and validation phases,we leveraged multiple external datasets containing over 2000 RCC cases from eight cohorts and one inhouse cohort to evaluate the accuracy of the TDERS.In addition,enrichment analysis,immune infiltration signatures,mutation landscape and therapy sensitivity between the high and low TDERS groups were compared.Finally,the impact of TDERS on the tumor microenvironment(TME)was also analysed in our single-cell datasets.Results:TDERS consisted of 12 mRNAs deregulated in both exosomes and tissues from patients with ccRCC.TDERS achieved satisfactory performance in both prognosis and immune checkpoint inhibitor(ICI)response across all ccRCC cohorts and other pathological types,since the average area under the curve(AUC)to predict 5-year overall survival(OS)was larger than 0.8 across the four cohorts.Patients in the TDERS high group were resistant to ICIs,while mercaptopurine might function as a promising agent for those patients.Patients with a high TDERS were characterized by coagulation and hypoxia,which induced hampered tumor antigen presentation and relative resistance to ICIs.In addition,single cells from 12 advanced samples validated this phenomenon since the interaction between dendritic cells and macrophages was limited.Finally,PLOD2,which is highly expressed in fibro-and epi-tissue,could be a potential ther

关 键 词：Renal cell carcinoma EXOSOME Non-invasive biopsy Immunotherapy response Multiomics PLOD2 

分 类 号：R73[医药卫生—肿瘤]