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

ABSTRACT: While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), its heterogeneous glycoproteome and dynamics with disease progression remain unmapped. Employing an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics on resected OSCC tissues, we firstly profiled the N-glycome that overall displayed uniform expression in OSCC patients with (N+, n = 19) and without (N0, n = 12) lymph node metastasis, suggesting relatively stable N-glycosylation during metastasis. Notably, glycoproteomics and advanced correlation analysis uncovered altered site-specific N-glycosylation and associations with clinicopathological features. Importantly, targeted analyses of the multi-omics data unveiled two N-glycans and three N-glycopeptides that were closely associated with patient survival. This study provides novel insight into the complex OSCC tissue N-glycoproteome forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glyco-markers for OSCC.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oral Cancer Cell

SUBMITTER: Adriana Franco Paes Leme

LAB HEAD: Adriana Franco Paes Leme

PROVIDER: PXD037134 | Pride | 2023-06-08

REPOSITORIES: Pride

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			Action	DRS
	200702_CC_T_FTHilic10_E1.raw	Raw
	200702_CC_T_FTHilic10_E2.raw	Raw
	200702_CC_T_FTHilic10_E3.raw	Raw
	200702_CC_T_FTHilic20_E1.raw	Raw
	200702_CC_T_FTHilic20_E2.raw	Raw

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Project description:Neutrophils are short-lived yet vital innate immune cells equipped with bioactive glycoproteins packed in cytosolic granules that can readily be mobilised to elicit an effective and timely response against invading pathogens. Since the dynamic glycosylation processes underpinning the dramatic metamorphosis associated with myeloid progenitor-to-neutrophil differentiation remain unmapped, we here perform a comprehensive spatiotemporal profiling of the complex N-glycoproteome of isolated granule populations from blood-derived neutrophils and during maturation of bone marrow-derived progenitors using glycomics-assisted glycoproteomics. Firstly, glycomics indicated that the granule populations of mature (resting) neutrophils exhibit distinctive glycophenotypes including, most strikingly, unusual paucimannosidic- and monoantennary complex-type N-glycans in azurophilic granules. The granule-specific N-glycosylation features were recapitulated by glycoproteomics, which also uncovered extensive site- and protein-specific N-glycosylation decorating 4,772 N-glycopeptides from 352 N-glycoproteins across the neutrophil granules. Excitingly, comprehensive mining of proteomics and transcriptomics data collected from discrete myeloid progenitor stages for glycopeptide and glyco-enzyme expression revealed that dramatic glycoproteome remodelling underpins the promyelocytic-to-metamyelocyte transition and that remodelling is driven predominantly by proteome expression changes rather than modulation of the glycosylation machinery. Notable exceptions were the oligosaccharyltransferase subunits responsible for initiation of N-glycoprotein biosynthesis that were strongly reduced with myeloid differentiation leading to reduced N-glycosylation efficiency in late-stage neutrophil maturation and in corresponding granules. Our study provides new spatiotemporal insights into the dynamic neutrophil N-glycoproteome, which exhibits intriguingly complex site-, protein- and granule-specific N-glycosylation features and which undergoes strong remodelling during myeloid progenitor-to-neutrophil metamorphosis.

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

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