Comprehensive Glycoprofiling of Oral Tumors 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), the heterogeneous and dynamic glycoproteome of tumor tissues from OSCC patients remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a cohort of resected primary tumor tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumor tissues displayed relatively uniform N-glycome profiles suggesting overall stable global N-glycosylation during disease progression, altered expression of six sialylated N-glycans was found to correlate with lymph node metastasis. Notably, glycoproteomics and advanced statistical analyses uncovered altered site-specific N-glycosylation revealing previously unknown associations with several clinicopathological features. Importantly, the glycomics and glycoproteomics data unveiled that comparatively high abundance of two core-fucosylated and sialylated N-glycans (Glycan 40a and Glycan 46a) and one N-glycopeptide from fibronectin were associated with low patient survival, while a relatively low abundance of N-glycopeptides from both afamin and CD59 were also associated with poor survival. This study provides insight into the complex OSCC tissue N-glycoproteome, thereby forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glycomarkers for OSCC.

Graphical Abstract

Highlights

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  Integrated glycomics and glycoproteomics analysis of oral tumor tissues.

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  First comprehensive map of the oral tumor N-glycoproteome.

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  Association of N-glycosylation with key clinicopathological features.

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  Specific N-glycans and N-glycopeptides report on patient survival.

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  Public resource to explore glycosylation-related mechanisms underpinning oral cancer.

In Brief

Powered by our comprehensive glycomics-assisted glycoproteomics approach, we here provide new insights into the heterogenous N-glycoproteome in oral cancer from patients with and without lymph node metastasis. We find evidence supporting previously unknown associations between glycosylation changes and important clinicopathological features including patient survival. The study and the publicly available glycomics and glycoproteomics data form an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glycomarkers for oral cancer.