A Glycosyltransferase-Related Signature for Predicting Overall Survival in Head and Neck Squamous Cell Carcinoma

Abstract

Background: Here, we establish a prognostic signature based on glycosyltransferase-related genes (GTRGs) for head and neck squamous cell carcinoma (HNSCC) patients. Methods: The prognostic signature of GTRGs was constructed via univariate and multivariate Cox analyses after obtaining the expression patterns of GTRGs from the TCGA. A nomogram based on the signature and clinical parameters was established to predict the survival of each HNSCC patient. Potential mechanisms were explored through gene set enrichment analysis (GSEA) and immune cell infiltration, immune checkpoints, immunotherapy, and tumor mutational burden (TMB) analyses. The expression differences and prognostic efficacy of the signature were verified through the gene expression omnibus (GEO) and several online databases. Results: The prognostic signature was constructed based on five glycosyltransferases (PYGL, ALG3, EXT2, FUT2, and KDELC1) and validated in the GSE65858 dataset. The pathways enriched in the high- and low-risk groups were significantly different. The high-risk group had higher tumor purity; lower infiltration of immune cells, such as CD8⁺ T cells and Tregs; higher cancer-associated fibroblast (CAF) infiltration; lower immune function; and lower checkpoint expression. The signature can also be applied to distinguish whether patients benefit from immunotherapy. In addition, the high-risk group had a higher TMB and more gene mutations, including those in TP53, CSMD1, CDKN2A, and MUC17. Conclusion: We propose a prognostic signature based on glycosyltransferases for HNSCC patients that may provide potential targets and biomarkers for the precise treatment of HNSCC.

Keywords: glycosyltransferase; head and neck squamous cell carcinoma; immune cell infiltration; prognostic signature; tumor mutational burden.