Single-Cell Proteomic Characterization of Drug-Resistant Prostate Cancer Cells Reveals Molecular Signatures...

Area of Science:

• Proteomics
• Cancer Biology
• Single-cell analysis

Background:

• Drug-resistant cells (DRCs) in prostate cancer drive therapeutic failure, relapse, and metastasis.
• Understanding the molecular basis of DRCs is crucial for developing effective treatments.
• Prostate cancer remains a significant health concern, necessitating research into resistance mechanisms.

Purpose of the Study:

• To characterize the proteomic landscape of prostate cancer drug-resistant cells (DRCs) using single-cell proteomics (SCP).
• To compare the proteomic profiles of DRCs with parental PC3 cells.
• To identify novel protein signatures and molecular targets associated with drug resistance and cancer progression.

Main Methods:

• Utilized an optimized high-throughput data-independent acquisition (DIA) approach for single-cell proteomics (SCP).
• Achieved robust protein quantification at the single-cell level, identifying over 1300 proteins per cell.
• Performed single-cell RNA-sequencing (scRNA-seq) for integrated molecular analysis.

Main Results:

• Identified distinct proteomic sub-clusters within the DRC population, correlated with cell size variations.
• Uncovered novel protein signatures involving cell adhesion, metabolic processes, surface proteins, and transcription factors.
• Detected six upregulated and 10 downregulated genes in drug-treated cells across both SCP and scRNA-seq platforms.

Conclusions:

• Prostate cancer drug-resistant cells exhibit significant heterogeneity and unique molecular signatures.
• The identified protein and gene alterations provide insights into DRC behavior and potential therapeutic vulnerabilities.
• This study offers valuable targets for overcoming therapeutic resistance in prostate cancer.