Proteomics Combined with N-Glycoproteomics to Explore the Pathogenesis of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) represents a malignant tumor linked to Epstein-Barr virus (EBV) that is characterized by distinctive, clinically relevant biological features. As protein N-glycosylation plays critical roles in cancer progression, we applied quantitative glycoproteomics to characterize NPC-specific glycosylation patterns. Using label-free proteomics and intact N-glycoproteomics, we analyzed 17 NPC tissues and 7 normal mucosal epithelia. Integrated analysis with PET/CT imaging and bioinformatics revealed correlations among differentially expressed glycoproteins, glycosyltransferases, and immunophenotypes. Functional validation demonstrated that MANEA, an enzyme linked to high-mannose glycosylation, influences NPC cell proliferation and migration. Furthermore, MANEA likely modulates PD-L1 expression through high-mannose glycans. Our findings indicate that high-mannose glycoproteins are predominant in NPC and may promote tumor progression not only by enhancing malignant behavior but also by facilitating immune escape via PD-L1 regulation, thereby impairing antitumor immunity.