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

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck cancer, comprising over 90% of all oral malignancies worldwide. The identification of diagnostic and prognostic markers for OSCC is crucial for improving patient outcomes, as early detection and treatment are critical for the successful management of this disease. Previously, we demonstrated that N-myc downstream-regulated gene 1 (NDRG1) and phosphoglycerate kinase 1 (PGK1) are prognostic markers for OSCC; however, their role in OSCC development remains unclear. To investigate this, we used TurboID-based proximity labeling to identify the interactomes of NDRG1 and PGK1 in HEK293 cells. Herein, protein abundance patterns from three time points were used for clustering 364 proteins with a "fast" or "slow" response to biotin. Of these, 65 proteins were also identified in neoplastic islands of OSCC patients from our previous study, and 28 of these proteins have their gene expression associated with prognostic features, including death, metastasis, and relapse. PRM-MS enabled the quantification of 17 of these proteins, providing further evidence of their presence in the OSCC prognostic interactome. Finally, we characterized a prognostic-associated interactome composed of 28 proteins, which enabled the prioritization of candidates that can be further explored in OSCC progression. The mass spectrometry data generated in this study have been deposited in ProteomeXchange with the data set identifier PXD048046.