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Series GSE193500 Query DataSets for GSE193500
Status Public on Jan 11, 2022
Title Modeling androgen deprivation therapy-induced prostate cancer dormancy and its clinical implications
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Purpose: Treatment-induced tumor dormancy is a state in cancer progression where residual disease is present but remains asymptomatic. Dormant cancer cells are treatment-resistant and responsible for cancer recurrence and metastasis. Prostate cancer (PCa) treated with androgen-deprivation therapy (ADT) often enters a dormant state. ADT-induced PCa dormancy remains poorly understood due to the challenge in acquiring clinical dormant PCa cells and the lack of representative models. We, therefore, aimed to develop clinically relevant models that can be used for studying ADT-induced PCa dormancy. Experimental design: Dormant PCa models were established by castrating mice bearing PCa patient-derived xenografts (PDXs) of hormonal naïve or sensitive PCa. Dormancy status and tumor relapse were monitored and evaluated. Paired pre- and post-castration (dormant) PDX tissues were subjected to morphological and transcriptome profiling analyses. Results: We established eleven ADT-induced dormant PCa models that closely mimicked the clinical courses of ADT-treated PCa. We identified two ADT-induced dormancy subtypes that differed in morphology, gene expression, and relapse rates. We discovered transcriptomic differences in pre-castration PDXs that predisposed the dormancy response to ADT. We further developed a dormancy subtype-based, predisposed gene signature that was significantly associated with ADT response in hormonal naïve PCa and clinical outcome in castration-resistant PCa treated with ADT or androgen-receptor pathway inhibitors.
 
Overall design Mice bearing patient-derived prostate cancer xenografts were surgically castrated. Tissues for microarray profiling and analyses were harvested at pre-castration and post-castration 12 week timepoints, respectively.
 
Contributor(s) Dong X, Xue H, Mo F, Lin Y, Lin D, Wong NK, Sun Y, Wilkinson S, Ku AT, Hao J, Ci X, Wu R, Haegert A, Silver R, Taplin M, Balk S, Alumkal JJ, Sowalsky AG, Gleave M, Collins C, Wang Y
Citation(s) 35082166
Submission date Jan 11, 2022
Last update date Apr 13, 2022
Contact name Yuzhuo Wang
Organization name University of British Columbia
Department Vancouver Prostate Centre
Lab The Living Tumor Laboratory
Street address 2660 Oak Street
City Vancouver
State/province BC
ZIP/Postal code V6H 3Z6
Country Canada
 
Platforms (1)
GPL14550 Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version)
Samples (22)
GSM5811596 LTL310_PRE
GSM5811597 LTL313B_PRE
GSM5811598 LTL313H_PRE
Relations
BioProject PRJNA796371

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE193500_RAW.tar 68.2 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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