Mapping the Interactome of OSCC Prognostic-Associated Proteins NDRG1 and PGK1 Through Proximity Labeling Using...

Area of Science:

• Oncology
• Proteomics
• Molecular Biology

Background:

• Oral squamous cell carcinoma (OSCC) is a major head and neck cancer, necessitating improved diagnostic and prognostic markers for better patient outcomes.
• Previous research identified N-myc downstream-regulated gene 1 (NDRG1) and phosphoglycerate kinase 1 (PGK1) as prognostic markers for OSCC, but their functional roles in disease development require further elucidation.

Purpose of the Study:

• To investigate the roles of NDRG1 and PGK1 in OSCC development by identifying their interacting protein partners.
• To characterize a prognostic-associated protein interactome in OSCC for potential biomarker discovery.

Main Methods:

• Utilized TurboID-based proximity labeling in HEK293 cells to map the interactomes of NDRG1 and PGK1.
• Analyzed protein abundance patterns across three time points to cluster proteins based on their response to biotin labeling.
• Integrated proteomic data with previous findings from OSCC neoplastic islands and correlated gene expression with prognostic features.

Main Results:

• Identified and clustered 364 proteins based on their proximity to NDRG1 and PGK1, categorizing them by response kinetics.
• Found 65 proteins common to both the interactome study and OSCC neoplastic islands.
• Characterized a prognostic-associated interactome of 28 proteins, with 17 quantified by PRM-MS, showing associations with OSCC patient outcomes (death, metastasis, relapse).

Conclusions:

• Successfully identified a prognostic-associated interactome for OSCC, providing a prioritized list of candidate proteins for further investigation.
• The characterized interactome offers potential new avenues for developing diagnostic and prognostic tools for oral squamous cell carcinoma.
• The study provides valuable proteomic data (PXD048046) for advancing OSCC research.