Related Experiment Video
Updated: Aug 1, 2025
Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
Published on: October 24, 2019
Integrative multi-omics and drug-response characterization of patient-derived prostate cancer primary cells
Ziruoyu Wang1, Yanan Li2, Wensi Zhao3,4
1Key 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.
Abstract:
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.
Insights
This study identifies Anterior Gradient 2 (AGR2) as a prognostic biomarker for prostate cancer (PCa). Diminished AGR2 enhances crizotinib
Area of Science:
- Oncology
- Genomics
- Proteomics
- Pharmacology
Background:
- Prostate cancer (PCa) is a leading global malignancy in men.
- Understanding protein-drug response relationships is crucial for precision PCa treatment.
- Existing PCa models lack comprehensive multi-omics and drug response data.
Purpose of the Study:
- To establish diverse Chinese PCa primary cell models for multi-omics analysis.
- To identify novel prognostic biomarkers and therapeutic targets for PCa.
- To investigate drug responses and underlying molecular mechanisms in PCa.
Main Methods:
- Establishment of 35 Chinese PCa primary cell models.
- Multi-omics analyses including gene mutations, mRNA, protein, and surface protein profiling.
- Drug library screening and pharmacoproteome analysis.
- In vitro (PC3 cell line) and in vivo (xenograft model) validation.
Main Results:
- Anterior Gradient 2 (AGR2) identified as a pre-operative prognostic biomarker for PCa.
- Crizotinib identified as a selective compound for malignant PCa primary cells.
- 14,372 significant protein-drug correlations discovered via pharmacoproteome analysis.
- Diminished AGR2 enhances crizotinib efficacy through ALK/c-MET-AKT axis activation.
Conclusions:
- Integrated multi-omics approach provides comprehensive understanding of PCa biomarkers.
- AGR2 serves as a valuable prognostic biomarker for prostate cancer.
- Crizotinib shows potential as a targeted therapy for PCa, especially with diminished AGR2.
- Findings enable more precise diagnosis and personalized therapeutic strategies for PCa.
