The Bioinformatics Identification of Potential Protein Glycosylation Genes Associated with a Glioma Stem Cell Signature

Abstract

Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma (GBM), which is the most malignant form of glioma. The implications and underlying mechanisms of protein glycosylation in GSC phenotypes and GBM malignancy are not fully understood. The implication of protein glycosylation and the corresponding candidate genes on the stem cell properties of GSCs and poor clinical outcomes in GBM were investigated, using datasets from the Gene Expression Omnibus, The Cancer Genome Atlas, and the Chinese Glioma Genome Atlas, accompanied by biological validation in vitro. N-linked glycosylation was significantly associated with GSC properties and the prognosis of GBM in the integrated bioinformatics analyses of clinical specimens. N-linked glycosylation was associated with the glioma grade, molecular biomarkers, and molecular subtypes. The expression levels of the asparagine-linked glycosylation (ALG) enzyme family, which is essential for the early steps in the biosynthesis of N-glycans, were prominently associated with GSC properties and poor survival in patients with GBM with high stem-cell properties. Finally, the oxidative phosphorylation pathway was primarily enriched in GSCs with a high expression of the ALG enzyme family. These findings suggest the role of N-linked glycosylation in the regulation of GSC phenotypes and GBM malignancy.

Keywords

• glioma stem cells
• glioblastoma
• protein glycosylation
• gene expression omnibus
• the cancer genome atlas
• chinese glioma genome atlas