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. 2023 Jul 18;16(7):1015-1025.
doi: 10.18240/ijo.2023.07.03. eCollection 2023.

Identification of hub genes for glaucoma: a study based on bioinformatics analysis and experimental verification

Rui-Ling Xie  1 , Hai-Yan Nie  1 , Yu-Xin Xu  2
Affiliations

Identification of hub genes for glaucoma: a study based on bioinformatics analysis and experimental verification

Rui-Ling Xie et al. Int J Ophthalmol. .

Abstract

Aim: To explore hub genes for glaucoma based on bioinformatics analysis and an experimental model verification.

Methods: In the Gene Expression Omnibus (GEO) database, the GSE25812 and GSE26299 datasets were selected to analyze differentially expressed genes (DEGs) by the GEO2R tool. Through bioinformatics analysis, 9 hub genes were identified. Receiver operating characteristic (ROC) curves and principal component analysis (PCA) were performed to verify whether the hub gene can distinguish glaucoma from normal eyes. The mouse model of glaucoma was constructed, and the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) assay was performed to detect the expression levels of hub genes in glaucoma.

Results: There were 128 overlapping DEGs in the GSE25812 and GSE26299 datasets, mainly involved in intracellular signalling, cell adhesion molecules and the Ras signalling pathway. A total of 9 hub genes were screened out, including GNAL, BGN, ETS2, FCGP4, MAPK10, MMP15, STAT1, TSPAN8, and VCAM1. The area under the curve (AUC) values of 9 hub genes were greater than 0.8. The PC1 axle could provide a 70.5% interpretation rate to distinguish glaucoma from normal eyes. In the ocular tissues of glaucoma in the mice model, the expression of BGN, ETS2, FCGR4, STAT1, TSPAN8, and VCAM1 was increased, while the expression of GNAL, MAPK10, and MMP15 was decreased.

Conclusion: Nine hub genes in glaucoma are identified, which may provide new biomarkers and therapeutic targets for glaucoma.

Keywords: biomarkers; glaucoma; hub genes.

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Figures

Figure 1
Figure 1. Normalization to samples in the GSE25812 and the GSE26299 datasets
A: Cross-comparability evaluation of data set samples in the GSE25812; B: Cross-comparability evaluation of data set samples in the GSE26299 dataset.
Figure 2
Figure 2. Identification of DEGs for glaucoma
A: Volcano plot of DEGs in the GSE25812 dataset. Red dots represent up-regulated genes in the group, and blue dots represent down-regulated genes in the group. B: Volcano plot of DEGs in the GSE26299 dataset. C: Heatmap of the up-regulated versus down-regulated genes ranked the top 25 in the GSE25812 dataset. Red represents highly expressed genes, and blue represents lowly expressed genes. D: Heatmap of the up-regulated versus down-regulated genes ranked the top 25 in the GSE26299 dataset. DEGs: Differentially expressed genes.
Figure 3
Figure 3. Venn diagram for overlapping DEGs in GSE25812 and GSE26299 dataset
DEGs: Differentially expressed genes.
Figure 4
Figure 4. GO annotations and KEGG pathways for overlapping genes
A: The top 6 items of the GO annotations are illustrated in a bubble plot. B: The top 8 KEGG pathways are illustrated in a bubble plot. GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes.
Figure 5
Figure 5. The PPI network of the overlapping DEGs
DEGs: Differentially expressed genes; PPI: Protein-protein interactions.
Figure 6
Figure 6. The hub modules of the overlapping DEGs
DEGs: Differentially expressed genes.
Figure 7
Figure 7. The expression abundance analysis of hub genes
The horizontal coordinates represent the amount of gene expression, the shape of the peaks indicates the dispersion between a set of data, and the vertical coordinates represent the number of samples corresponding to the amount of gene expression.
Figure 8
Figure 8. ROC curve analysis of key genes
A: GNAL; B: BGN; C: ETS2; D: FCGP4; E: MAPK10; F: MMP15; G: STAT1; H: TSPAN8; I: VCAM1. ROC: Receiver operating characteristic.
Figure 9
Figure 9. PCA analysis of key genes
The coordinate axes PC1 and PC2 of the plot are the first and second principal components (rate of variance explained by latent variables). Dots represent samples and different colors indicate different groupings. PCA: Principal component analysis.
Figure 10
Figure 10. Histological changes in glaucoma was observed by HE staining
HE staining: Hematoxylin-eosin staining.
Figure 11
Figure 11. Validation of mRNA expression of 9 hub genes
A: RT-qPCR to detect mRNA expression levels of GNAL. B: BGN. C: ETS2. D: FCGR4. E: MAPK10; F: MMP15; G: STAT1; H: TSPAN8; I: VCAM1. aP<0.05, bP<0.01, cP<0.001. RT-qPCR: Real-time reverse transcriptase-polymerase chain reaction; GLC: Glaucoma.
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References

    1. Zukerman R, Harris A, Oddone F, Siesky B, Verticchio Vercellin A, Ciulla TA. Glaucoma heritability: molecular mechanisms of disease. Genes. 2021;12(8):1135. - PMC - PubMed
    1. Kang JM, Tanna AP. Glaucoma. Med Clin North Am. 2021;105(3):493–510. - PubMed
    1. Saha BC, Kumari R, Sinha BP, Ambasta A, Kumar S. Lasers in glaucoma: an overview. Int Ophthalmol. 2021;41(3):1111–1128. - PubMed
    1. Lim R. The surgical management of glaucoma: a review. Clin Exp Ophthalmol. 2022;50(2):213–231. - PubMed
    1. Mehran NA, Sinha S, Razeghinejad R. New glaucoma medications: latanoprostene bunod, netarsudil, and fixed combination netarsudil-latanoprost. Eye (Lond) 2020;34(1):72–88. - PMC - PubMed

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