Comprehensive Glycoprofiling of Oral Tumors Associates N-Glycosylation With Lymph Node Metastasis and Patient Survival

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Carnielli, Carolina Moretto ; Morais, Thayna Melo de Lima ; Patroni, Fabio Malta de Sa ; Ribeiro, Ana Carolina Prado ; Brandao, Thais Bianca ; Sobroza, Evandro ; Matos, Leandro Luongo ; Kowalski, Luiz Paulo ; Leme, Adriana Franco Paes ; Kawahara, Rebeca ; Thaysen-Andersen, Morten

• Document type: Journal article
• Source: MOLECULAR & CELLULAR PROTEOMICS; v. 22, n. 7, p. 19-pg., 2023-07-01.

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 Nglycosylation 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 Nglycoproteome, thereby forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glycomarkers for OSCC. (AU)

• FAPESP's process: 18/02180-0 - Study of the glycoprotein composition in the surface of extracellular vesicles of plasma from patients with oral cancer and its correlation to prognosis
• Grantee: Carolina Moretto Carnielli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/18496-6 - The role of alcohol treated-extracellular vesicles in oral cells transformation
• Grantee: Adriana Franco Paes Leme
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/17840-8 - Ultra-deep glycome and glycoproteome profiling of oral cancer cells, tissues and extracellular vesicles to uncover new prognostic signatures
• Grantee: Carolina Moretto Carnielli
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor