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

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

机构地区：[1]Key Laboratory of Metabolism and Molecular Medicine,The Ministry of Education,Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Shanghai Medical College,Fudan University,200032,Shanghai,China [2]CAS Key Lab of Separation Sciences for Analytical Chemistry,National Chromatographic Research and Analysis Center,Dalian Institute of Chemical Physics,Chinese Academy of Sciences,116023,Dalian,China [3]The Chemical Proteomics Center and State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,201203,Shanghai,China [4]University of Chinese Academy of Sciences,100049,Beijing,China [5]Department of Urology,Zhongshan Hospital,Fudan University,200032,Shanghai,China [6]Department of Urology,Zhongshan Hospital Wusong Branch,Fudan University,200032,Shanghai,China [7]Center for Novel Target and Therapeutic Intervention,Chongqing Medical University,400016,Chongqing,China [8]Department of Urology,Huashan Hospital,Fudan University,200040,Shanghai,China

出　　处：《Signal Transduction and Targeted Therapy》2023年第6期3013-3028,共16页信号转导与靶向治疗（英文）

基　　金：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.]).

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.

关 键 词：DRUG PC3 diagnosis OPERATIVE 

分 类 号：R737.25[医药卫生—肿瘤]