(0628) Correlation of Terminal Glycosylation Genes FUT2 and ST3GAL1 With Head and Neck Tumor Differentiation

Introduction: Head and neck cancer (HNC) leads to over 350,000 deaths globally and over 13,000 in the US annually. Recurrent and treatment-resistant disease contribute to high mortality rates, suggesting that new approaches are needed to monitor for recurrence, and identify new therapeutic targets. This study explores an underappreciated aspect of HNC—glycosylation, a protein modification with known involvement in receptor tyrosine kinase (RTK) signaling, tumor cell adhesion, epithelial-to-mesenchymal transition (EMT), and aggressive tumor cell phenotypes. Prior research has associated terminal glycosylation events, such as fucosylation, with HNC prognosis. Specifically, higher α1, 2-fucosyltransferase FUT2 expression is associated with increased survival in HNC patients.

Methods: Here, a secondary genomic analysis of 138 HNC tumors was performed, utilizing a multivariate hierarchical regression model to examine the relationship between glycosyltransferase gene (FUT2, FUT3, ST3GAL1) expression and tumor differentiation.

Results: FUT2 and ST3GAL1 remained predictors of tumor differentiation, explaining 21% of the variance in tumor differentiation (F = 2.760, p = 0.009). Higher ST3GAL1 expression was associated with poor tumor differentiation (Beta = 0.362, p < 0.001) while higher FUT2 expression was associated with well differentiated tumors (Beta = -0.277, p = 0.042). A negative correlation between FUT2 expression and tumor differentiation suggests FUT2 expression is associated with a favorable prognosis. In contrast, elevated ST3GAL1 expression correlates with poor differentiation.

Conclusions: These findings may inform the development of surveillance glycoprotein biomarkers by revealing insights into effective surveillance strategies through the correlation with glycosyltransferase gene expression and tumor differentiation. Glycosyltransferases' role in HNC suggests potential as therapeutic targets, indicating novel interventions for these enzymes or their products.