A novel in vitro prognostic model of bladder cancer based on urine-derived living tumor cells

查看全文 作　　者：Jiaqi [1,2]Wang;Jiying [1,3]Zhu;Junchi [4]Hu;Ziruoyu [1]Wang;Xiaobo [1]Wang;Jianbo [4]Pan;Yiwei [2]Chu;Zengxia [1]Li;Wei [1]Jiang;Chunmin [3]Liang;Jun [5]Hou;Jianming [6]Guo;Yongjun [1,4]Dang;Shuai [6,7]Jiang 机构地区：[1]Key Laboratory of Metabolism and Molecular Medicine,Ministry of Education and Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China;[2]Department of Immunology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China;[3]Laboratory of Tumor Immunology,Department of Anatomy,Histology,and Embryology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China;[4]Center for Novel Target and Therapeutic Intervention,Chongqing Medical University,Chongqing 400016,China;[5]Department of Pathology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;[6]Department of Urology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;[7]Department of Urology,Zhongshan Hospital Wusong Branch,Fudan University,Shanghai 200940,China 出　　处：《Genes & Diseases》索引2023年第10卷第6期,共11页 基　　金：supported by the National Natural Science Foundation of China(No.82073413 to S.J.);the Clinical and Research Fund of Wu Jieping Medical Foundation(No.320.6750.2020-01-12 to S.J.);the National Natural Science Foundation of China(No.22137002 to Y.D.);the China Postdoctoral Science Foundation(No.2020TQ0068 to J.W.). 摘　　要：Bladder cancer(BLCA)remains a difficult malignancy to manage because of its high recurrence,intense follow-up,and invasive diagnostic and treatment techniques.Immune checkpoint inhibitors(ICIs)have forged a new direction for the treatment of BLCA,but it is currently challenging to predict whether an individual patient will be sensitive to ICIs.We collected 43 urine/tumor samples from BLCA patients for primary bladder cancer cells(BCCs)culturing using our previously reported BCC culture platform.We used flow cytometry(FCM)to measure the expression levels of Programmed Death-Ligand 1(PD-L1)on BCCs before and after interferon-gamma(IFN-γ)treatment and found that PD-L1 expression and the sensitivities to IFN-γvaried among patients.RNA-sequencing,western blotting,and programmed death-1(PD-1)binding assays confirmed that the BCC FCM-based PD-L1 detection platform(BC-PD-L1)was reliable and was not hindered by the glycosylation of PD-L1.In the subsequent retrospective study,we found that IFN-γ-stimulated PD-L1(sPD-L1)expression on BCCs detected by BC-PD-L1 could predict the prognosis of BLCA patients.Importantly,the prognostic value was similar or even better in urine-derived BC-PD-L1(UBC-PD-L1).Transcriptome analysis showed that BCCs with high sPD-L1 tended to enrich genes associated with the collagen-containing extracellular matrix,cell–cell adhesion,and positive regulation of the immune system.In addition,the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients.In conclusion,as a novel personalized urine-detection method,UBC-PD-L1 may provide a rapid,accurate,and non-invasive tool for monitoring tumor progression,predicting therapeutic responses,and helping improve BLCA clinical treatment in future. 关 键 词：Bladder cancer Immune checkpoint inhibitors Predictive model Primary cells URINE