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

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 proteomic basis of DRCs is crucial for developing effective treatments.

Purpose of the Study:

• To characterize the proteomic landscape of prostate cancer drug-resistant cells (DRCs) at the single-cell level.
• To compare the proteomic profiles of DRCs with parental PC3 cells.
• To identify novel protein signatures and potential therapeutic targets in DRCs.

Main Methods:

• Employed an optimized high-throughput Data Independent Acquisition (DIA) approach for single-cell proteomics (SCP).
• Achieved a throughput of 60 samples per day for robust protein quantification.
• Integrated SCP data with single-cell RNA sequencing (scRNA-seq) data.

Main Results:

• Identified over 1,300 proteins per cell on average, revealing distinct proteomic sub-clusters within DRCs.
• Discovered novel protein signatures related to cell adhesion, metabolism, surface proteins, and transcription factors.
• Found six upregulated and ten downregulated genes consistently altered 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 offer insights into DRC behavior and potential therapeutic strategies.
• This study provides a foundation for targeting DRCs to overcome treatment resistance in prostate cancer.