Screening of Primary Open-Angle Glaucoma Diagnostic Markers based on Immune-related Genes and Immune Infiltration

Abstract PURPOSE. Primary open-angle glaucoma (POAG) continues to be a poorly understood disease. Performing bioinformatics analyses of optic nerve (ON) and trabecular meshwork (TM) gene expression data in order to further elucidate the immune-related genes of POAG and identify candidate target genes for treatment.METHODS. We performed a gene analysis of publicly available microarray data, namely, the GSE27276-GPL2507, GSE2378-GPL8300, GSE9944-GPL8300, GSE9944-GPL571 datasets from Gene Expression Omnibus database. The obtained datasets were used as input for parallel pathway analyses. Based on Random Forest and Support vector machine (SVM) analysis to screen the key genes, significantly changed pathways were clustered into functional categories and the results were further investigated. CIBERSORT was used to evaluate infiltration of immune cells in POAG tissues. A network visualizing the differences between the POAG and normal was created. GO and KEGG enrichment analyses were performed using the Metascape database. We divided the differential mRNA into up-regulated and down-regulated groups, and predicted the drug targeting of the differential genes through the Connectivity Map (CMap) database.RESULTS. A total of 49 differentially expressed genes, including 19 downregulated genes and 30 upregulated genes, were detected. Five genes (KRT14, HBB, ACOX2, HEPH and KRT13) were significantly changed. The results showed that the expression profiles of drug disturbances such as avrainvillamide-analysis-3, cytochalasin-D, NPI-2358, oxymethylone and vinorelbine were negatively correlated with the expression profiles of disease disturbances. It indicated that these drugs may reduce or even reverse the POAG disease state.CONCLUSION. This study provides an overview of the processes involved in the molecular pathogenesis of POAG in the ON and TM. The findings provide a new understanding of the molecular mechanism of POAG from the perspective of immunology.