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

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR & CELLULAR PROTEOMICS; v. 22, n. 7, p. 19-pg., 2023-07-01.

Resumo

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)

• Processo FAPESP: 18/02180-0 - Estudo da composição de glicoproteínas na superfície de vesículas extracelulares de plasma de pacientes com câncer de boca e sua correlação com o prognóstico
• Beneficiário: Carolina Moretto Carnielli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/18496-6 - O papel do álcool na transformação de células orais mediada por vesículas extracelulares
• Beneficiário: Adriana Franco Paes Leme
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/17840-8 - Caracterização do glicoma e do glicoproteoma de células, tecidos e vesículas extracelulares de câncer oral para a descoberta de novas assinaturas de prognóstico
• Beneficiário: Carolina Moretto Carnielli
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado