Identification of immune-related biomarkers for glaucoma using gene expression profiling

Dangdang Wang; Yanyu Pu; Sisi Tan; Xiaochen Wang; Lihong Zeng; Junqin Lei; Xi Gao; Hong Li

doi:10.3389/fgene.2024.1366453

Identification of immune-related biomarkers for glaucoma using gene expression profiling

Front Genet. 2024 Apr 17:15:1366453. doi: 10.3389/fgene.2024.1366453. eCollection 2024.

Authors

Dangdang Wang^#^{1

2}, Yanyu Pu^#^{1

2}, Sisi Tan^{1

2}, Xiaochen Wang^{1

2}, Lihong Zeng^{1

2}, Junqin Lei^{1

2}, Xi Gao^{1

2}, Hong Li^{1

2}

Affiliations

¹ Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.

^# Contributed equally.

Abstract

Introduction: Glaucoma, a principal cause of irreversible vision loss, is characterized by intricate optic neuropathy involving significant immune mechanisms. This study seeks to elucidate the molecular and immune complexities of glaucoma, aiming to improve our understanding of its pathogenesis. Methods: Gene expression profiles from glaucoma patients were analyzed to identify immune-related differentially expressed genes (DEGs). Techniques used were weighted gene co-expression network analysis (WGCNA) for network building, machine learning algorithms for biomarker identification, establishment of subclusters related to immune reactions, and single-sample gene set enrichment analysis (ssGSEA) to explore hub genes' relationships with immune cell infiltration and immune pathway activation. Validation was performed using an NMDA-induced excitotoxicity model and RT-qPCR for hub gene expression measurement. Results: The study identified 409 DEGs differentiating healthy individuals from glaucoma patients, highlighting the immune response's significance in disease progression. Immune cell infiltration analysis revealed elevated levels of activated dendritic cells, natural killer cells, monocytes, and immature dendritic cells in glaucoma samples. Three hub genes, CD40LG, TEK, and MDK, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the NMDA-induced excitotoxicity model. Discussion: The findings propose the three identified immune-related genes (IRGs) as novel diagnostic markers for glaucoma, offering new insights into the disease's pathogenesis and potential therapeutic targets. The strong correlation between these IRGs and immune responses underscores the intricate role of immunity in glaucoma, suggesting a shift in the approach to its diagnosis and treatment.

Keywords: WGCNA; biomarkers; glaucoma; immune cell infiltration; immune-related genes; machine learning; subclusters.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was funded by grant (81974131) from National Natural Science Foundation of China.