Identification of Glycosylation-Related Gene Signatures in Astrocytes from Glaucoma Using GEO Datasets

DOI: https://doi.org/10.62517/jmhs.202505404

Author(s)

Dingqiao Wang1,3, Minyi Zhu2, Peidong Yuan2, Yiyu Xie2, Bingying Lin3, Hongzhi Yuan2,*

Affiliation(s)

1Department of Ophthalmology, the Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China 2Department of Ophthalmology, the Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China 3State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science; Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China. *Corresponding Author

Abstract

Glycosylation critically regulates protein folding, stability, and cellular signaling in neurodegenerative disorders; however, its role in glaucoma pathogenesis remains underexplored. We aimed to investigate differentially expressed glycosylation-related genes (GRGs) in glaucoma astrocytes and explore their connections with immune responses, an aspect that has not been systematically addressed in prior computational studies. We integrated two glaucoma-related microarray datasets (GSE2378 and GSE9944) comprising 13 glaucoma and 42 control human astrocyte samples. Differential expression analysis and functional enrichment assessments were conducted using standard bioinformatics approaches. We developed protein–protein interaction networks, identified essential genes, and evaluated immune-related gene expression through single-sample Gene Set Enrichment Analysis (GSEA). The study identified 42 differentially expressed GRGs and seven hub genes (SEC23A, BET1, ARCN1, COPB2, VCP, UBC, and SEC61B) involved in protein trafficking and secretory pathway regulation. Functional analysis revealed significant enrichment in glycoprotein metabolic processes and inflammatory pathways. GSEA highlighted the involvement of Wnt/β-catenin signaling and interleukin-23 pathways. Six hub genes demonstrated substantial diagnostic capacity. Analysis of Immune cell infiltration revealed significant alterations in eight immune cell populations, with activated CD4+ T cells showing positive correlations with all hub genes. These findings suggest that astrocyte glycosylation contributes to glaucoma progression and may be associated with immune dysregulation, providing new insights into disease pathogenesis and identifying potential diagnostic biomarkers and therapeutic targets.

Keywords

Glaucoma; Glycosylation-Related Genes; Bioinformatics; Immune Cell Infiltration; Astrocyte Dysfunction

References

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