Comprehensive glycoprofiling of oral tumours associatesN-glycosylation with lymph node metastasis and patient survival

While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), its heterogeneous glycoproteome and dynamics with disease progression remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a valuable cohort of resected tumour tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumour tissues displayed uniformN-glycome profiles suggesting relatively stable globalN-glycosylation during lymph node metastasis, glycoproteomics and advanced correlation analysis notably uncovered altered site-specificN-glycosylation and previously unknown associations with several key clinicopathological features. Importantly, focused analyses of the multi-omics data unveiled twoN-glycans and threeN-glycopeptides that were closely associated with patient survival. This study provides novel insight into the complex OSCC tissueN-glycoproteome forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glyco-markers for OSCC.TeaserDeep survey of the dynamic landscape of complex sugars in oral tumours paves a way for new prognostic disease markers.