Integrative multi-omics and drug-response characterization of patient-derived prostate cancer primary cells

作者全名："Wang, Ziruoyu; Li, Yanan; Zhao, Wensi; Jiang, Shuai; Huang, Yuqi; Hou, Jun; Zhang, Xuelu; Zhai, Zhaoyu; Yang, Chen; Wang, Jiaqi; Zhu, Jiying; Pan, Jianbo; Jiang, Wei; Li, Zengxia; Ye, Mingliang; Tan, Minjia; Jiang, Haowen; Dang, Yongjun"

作者地址："[Wang, Ziruoyu; Wang, Jiaqi; Zhu, Jiying; Jiang, Wei; Li, Zengxia; Dang, Yongjun] Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Biochem & Mol Biol,Minist Educ,Key Lab Metab, Shanghai 200032, Peoples R China; [Li, Yanan; Ye, Mingliang] Chinese Acad Sci, Dalian Inst Chem Phys, Natl Chromatog Res & Anal Ctr, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China; [Zhao, Wensi; Huang, Yuqi; Tan, Minjia] Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai 201203, Peoples R China; [Zhao, Wensi; Huang, Yuqi; Tan, Minjia] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; [Zhao, Wensi; Huang, Yuqi] Univ Chinese Acad Sci, Beijing 100049, Peoples R China; [Jiang, Shuai; Hou, Jun] Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai 200032, Peoples R China; [Jiang, Shuai] Fudan Univ, Zhongshan Hosp, Dept Urol, Wusong Branch, Shanghai 200032, Peoples R China; [Zhang, Xuelu; Zhai, Zhaoyu; Pan, Jianbo; Dang, Yongjun] Chongqing Med Univ, Ctr Novel Target & Therapeut Intervent, Chongqing 400016, Peoples R China; [Yang, Chen; Jiang, Haowen] Fudan Univ, Huashan Hosp, Dept Urol, Shanghai 200040, Peoples R China"

通信作者："Dang, YJ (通讯作者)，Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Biochem & Mol Biol,Minist Educ,Key Lab Metab, Shanghai 200032, Peoples R China.; Ye, ML (通讯作者)，Chinese Acad Sci, Dalian Inst Chem Phys, Natl Chromatog Res & Anal Ctr, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China.; Tan, MJ (通讯作者)，Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai 201203, Peoples R China.; Tan, MJ (通讯作者)，Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China.; Dang, YJ (通讯作者)，Chongqing Med Univ, Ctr Novel Target & Therapeut Intervent, Chongqing 400016, Peoples R China.; Jiang, HW (通讯作者)，Fudan Univ, Huashan Hosp, Dept Urol, Shanghai 200040, Peoples R China."

来源：SIGNAL TRANSDUCTION AND TARGETED THERAPY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000978636600001

JCR分区：Q1

影响因子：40.8

年份：2023

卷号：8

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Prostate cancer (PCa) is the second most prevalent malignancy in males across the world. A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa. Herein, we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients, including gene mutations, mRNA/protein/surface protein distributions, and pharmaceutical responses. The multi-omics analyses identify Anterior Gradient 2 (AGR2) as a pre-operative prognostic biomarker in PCa. Through the drug library screening, we describe crizotinib as a selective compound for malignant PCa primary cells. We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations. Surprisingly, the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model. Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses, allowing for more precise diagnosis and therapies."

基金机构："National Natural Science Foundation of China [22137002, 32071432, 81872102]; University Innovation Research Group Project of Chongqing [CXQT21016]; High-Level Innovation Platform Project of Chongqing; Talent Program of Chongqing [CQYC202003053]; collaborative project of Chinese Academy of Sciences institutions and universities in Chongqing [HZ2021006]; Innovative Research Team of High-Level Local Universities in Shanghai [SSMU-ZDCX20181202]"

基金资助正文："This work was supported by National Natural Science Foundation of China (22137002 [Y.D.], 32071432 [M.T.], 81872102 [H.J.]); University Innovation Research Group Project of Chongqing (CXQT21016 [Y.D.]); High-Level Innovation Platform Project of Chongqing [Y.D.]; Talent Program of Chongqing (CQYC202003053 [Y.D.]); The collaborative project of Chinese Academy of Sciences institutions and universities in Chongqing (HZ2021006 [Y.D.]); Innovative Research Team of High-Level Local Universities in Shanghai (SSMU-ZDCX20181202 [M.T.])."