Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting

In this study, we integrated proteomic and phosphoproteomic analyses of NPC tissues and normal nasopharyngeal tissues to systematically identify key dysregulated protein networks, which are enriched in genes associated with cell cycle, cilium function, immune response, metabolism, mTOR signaling, and responses to virus infection.

Based on these proteomic characteristics, we classified NPC into two molecular subtypes, subtype 1 and 2, which exhibit significant clinical heterogeneity. Moreover, we identify protein signatures for both normal and cancerous tissues, as well as for the two molecular subtypes, and developed diagnostic and prognostic models. Through computational drug repurposing and experimental validation, we identified the pan-histone deacetylase inhibitor Panobinostat as a potent anti-tumor agent for NPC in both in vitro and in vivo models.