Author:
Suo Lingge,Dai Wanwei,Qin Xuejiao,Li Guanlin,Zhang Di,Cheng Tian,Yao Taikang,Zhang Chun
Abstract
Abstract
Purpose
Primary open-angle glaucoma (POAG) continues to be a poorly understood disease. Although there were multiple researches on the identification of POAG biomarkers, few studies systematically revealed the immune-related cells and immune infiltration of POAG. Bioinformatics analyses of optic nerve (ON) and trabecular meshwork (TM) gene expression data were performed 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, and GSE9944-GPL571 datasets from the 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 the infiltration of immune cells in POAG tissues. A network visualizing the differences between the data in the POAG and normal groups was created. GO and KEGG enrichment analyses were performed using the Metascape database. We divided the differentially expressed mRNAs into upregulated and downregulated groups and predicted the drug targets of the differentially expressed 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 ((Keratin 14) KRT14, (Hemoglobin subunit beta) HBB, (Acyl-CoA Oxidase 2) ACOX2, (Hephaestin) HEPH and Keratin 13 (KRT13)) were significantly changed. The results showed that the expression profiles of drug disturbances, including those for avrainvillamide-analysis-3, cytochalasin-D, NPI-2358, oxymethylone and vinorelbine, were negatively correlated with the expression profiles of disease disturbances. This finding 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.
Funder
Peking University Medicine Fund of Fostering Young Scholars’ Scientific & Technological Innovation
Chinese State Natural Science Foundation
National Science and Technology Infrastructure Program
Capital’s Funds for Health Improvement and Research of China
Publisher
Springer Science and Business Media LLC
Subject
Health Informatics,Genetics
Cited by
1 articles.
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