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Updated: Jun 23, 2025
Phosphopeptide Enrichment Coupled with Label-free Quantitative Mass Spectrometry to Investigate the Phosphoproteome in Prostate Cancer
Published on: August 2, 2018
Proteomic profiling of prostate cancer reveals molecular signatures under antiandrogen treatment
Yurun Huang1, Guanglin Yang2, Xinpeng Yao3
1Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
Background:
Tumorigenesis and progression of prostate cancer (PCa) are indispensably dependent on androgen receptor (AR). Antiandrogen treatment is the principal preference for patients with advanced PCa. However, the molecular characteristics of PCa with antiandrogen intervention have not yet been fully uncovered.
Methods:
We first performed proteome analysis with 32 PCa tumor samples and 10 adjacent tissues using data-independent acquisition (DIA)- parallel accumulation serial fragmentation (PASEF) proteomics. Then label-free quantification (LFQ) mass spectrometry was employed to analyze protein profiles in LNCaP and PC3 cells.
Results:
M-type creatine kinase CKM and cartilage oligomeric matrix protein COMP were demonstrated to have the potential to be diagnostic biomarkers for PCa at both mRNA and protein levels. Several E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) were significantly altered in PCa and PCa cells under enzalutamide treatment, and these proteins might reprogram proteostasis at protein levels in PCa. Finally, we discovered 127 significantly varied proteins in PCa samples with antiandrogen therapy and further uncovered 4 proteins in LNCaP cells upon enzalutamide treatment.
Conclusions:
Our research reveals new potential diagnostic biomarkers for prostate cancer and might help resensitize resistance to antiandrogen therapy.
Insights
This study identifies new biomarkers for prostate cancer (PCa) and explores molecular changes in PCa cells treated with antiandrogen therapy. Findings may help overcome resistance to these treatments.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Prostate cancer (PCa) progression relies on the androgen receptor (AR).
- Antiandrogen therapy is standard for advanced PCa, but its molecular effects are not fully understood.
Purpose of the Study:
- To uncover molecular characteristics of PCa under antiandrogen intervention.
- To identify novel diagnostic biomarkers for PCa.
- To investigate mechanisms of resistance to antiandrogen therapy.
Main Methods:
- Proteome analysis of 32 PCa tumor samples and 10 adjacent tissues using DIA-PASEF.
- Label-free quantification (LFQ) mass spectrometry on LNCaP and PC3 cells.
- Analysis of protein profiles in PCa cells with and without enzalutamide treatment.
Main Results:
- M-type creatine kinase (CKM) and cartilage oligomeric matrix protein (COMP) show potential as PCa diagnostic biomarkers at mRNA and protein levels.
- Significant alterations in E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) suggest proteostasis reprogramming in PCa.
- 127 proteins varied significantly in PCa samples with antiandrogen therapy; 4 proteins were identified in LNCaP cells upon enzalutamide treatment.
Conclusions:
- New potential diagnostic biomarkers for prostate cancer were identified.
- The study provides insights that may help resensitize prostate cancer to antiandrogen therapy.
