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

作者全名："Wang, Jiaqi; Zhu, Jiying; Hu, Junchi; Wang, Ziruoyu; Wang, Xiaobo; Pan, Jianbo; Chu, Yiwei; Li, Zengxia; Jiang, Wei; Liang, Chunmin; Hou, Jun; Guo, Jianming; Dang, Yongjun; Jiang, Shuai"

作者地址："[Wang, Jiaqi; Zhu, Jiying; Wang, Ziruoyu; Wang, Xiaobo; Li, Zengxia; Jiang, Wei; Dang, Yongjun] Fudan Univ, Key Lab Metab & Mol Med, Minist Educ, Shanghai 200032, Peoples R China; [Wang, Jiaqi; Zhu, Jiying; Wang, Ziruoyu; Wang, Xiaobo; Li, Zengxia; Jiang, Wei; Dang, Yongjun] Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Shanghai 200032, Peoples R China; [Wang, Jiaqi; Chu, Yiwei] Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai 200032, Peoples R China; [Zhu, Jiying; Liang, Chunmin] Fudan Univ, Sch Basic Med Sci, Dept Anat Histol & Embryol, Lab Tumor Immunol, Shanghai 200032, Peoples R China; [Hu, Junchi; Pan, Jianbo; Dang, Yongjun] Chongqing Med Univ, Ctr Novel Target & Therapeut Intervent, Chongqing 400016, Peoples R China; [Hou, Jun] Fudan Univ, Zhongshan Hosp, Dept Pathol, Shanghai 200032, Peoples R China; [Guo, Jianming; Jiang, Shuai] Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai 200032, Peoples R China; [Jiang, Shuai] Fudan Univ, Zhongshan Hosp, Wusong Branch, Dept Urol, Shanghai 200940, Peoples R China; [Jiang, Shuai] Fudan Univ, Zhongshan Hosp, Dept Orthopaed Surg, 180 Fenglin Rd, Shanghai 200032, Peoples R China; [Jiang, Shuai] Fudan Univ, Zhongshan Hosp, Dept Urol, Wusong Branch, 216 Mudanjiang Rd, Shanghai 200032, Peoples R China; [Dang, Yongjun] Chongqing Med Univ, Ctr Novel Target & Therapeut Intervent, 1 Med Sch Rd, Chongqing 400016, Peoples R China; [Guo, Jianming] Fudan Univ, Zhongshan Hosp, Dept Urol, 180 Fenglin Rd, Shanghai 200032, Peoples R China; [Hou, Jun] Fudan Univ, Zhongshan Hosp, Dept Pathol, 180 Fenglin Rd, Shanghai 200032, Peoples R China; [Liang, Chunmin] Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Anat, 131 Dongan Rd, Shanghai 200032, Peoples R China"

通信作者："Jiang, S (通讯作者)，Fudan Univ, Zhongshan Hosp, Dept Orthopaed Surg, 180 Fenglin Rd, Shanghai 200032, Peoples R China.; Jiang, S (通讯作者)，Fudan Univ, Zhongshan Hosp, Dept Urol, Wusong Branch, 216 Mudanjiang Rd, Shanghai 200032, Peoples R China.; Dang, YJ (通讯作者)，Chongqing Med Univ, Ctr Novel Target & Therapeut Intervent, 1 Med Sch Rd, Chongqing 400016, Peoples R China.; Guo, JM (通讯作者)，Fudan Univ, Zhongshan Hosp, Dept Urol, 180 Fenglin Rd, Shanghai 200032, Peoples R China.; Hou, J (通讯作者)，Fudan Univ, Zhongshan Hosp, Dept Pathol, 180 Fenglin Rd, Shanghai 200032, Peoples R China.; Liang, CM (通讯作者)，Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Anat, 131 Dongan Rd, Shanghai 200032, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001052663000001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：10

期号：6

开始页：2586

结束页：2596

文献类型：Article

关键词：Bladder cancer; Immune checkpoint; Predictive model; Primary cells; Urine

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-g) treatment and found that PD-L1 expression and the sensitivities to IFN-g varied 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-PDL1) was reliable and was not hindered by the glycosylation of PD-L1. In the subsequent retrospective study, we found that IFN-g-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. 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons."

基金机构：National Natural Science Foundation of China [320.6750.2020-01-12]; Clinical and Research Fund of Wu Jieping Medical Foundation [2020TQ0068]; China Postdoctoral Science Foundation; [22137002]

基金资助正文："<BOLD>Funding</BOLD> This work was 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.) , and the China Postdoctoral Science Foundation (No. 2020TQ0068 to J.W.) ."