Purpose: Glaucoma is the second commonest cause of blindness. We assessed the gene expression profile of astrocytes in the optic nerve head to identify possible prognostic biomarkers for glaucoma.
Method: A total of 20 patient and nine normal control subject samples were derived from the GSE9944 (six normal samples and 13 patient samples) and GSE2378 (three normal samples and seven patient samples) datasets, screened by microarray-tested optic nerve head tissues, were obtained from the Gene Expression Omnibus (GEO) database. We used a weighted gene coexpression network analysis (WGCNA) to identify coexpressed gene modules. We also performed a functional enrichment analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Genes expression was represented by boxplots, functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all the key genes. Then the key genes were validated by the external dataset.
Results: A total 8,606 genes and 19 human optic nerve head samples taken from glaucoma patients in the GSE9944 were compared with normal control samples to construct the co-expression gene modules. After selecting the most common clinical traits of glaucoma, their association with gene expression was established, which sorted two modules showing greatest correlations. One with the correlation coefficient is 0.56 (P = 0.01) and the other with the correlation coefficient is -0.56 (P = 0.01). Hub genes of these modules were identified using scatterplots of gene significance versus module membership. A functional enrichment analysis showed that the former module was mainly enriched in genes involved in cellular inflammation and injury, whereas the latter was mainly enriched in genes involved in tissue homeostasis and physiological processes. This suggests that genes in the green-yellow module may play critical roles in the onset and development of glaucoma. A LASSO regression analysis identified three hub genes: Recombinant Bone Morphogenetic Protein 1 gene (BMP1), Duchenne muscular dystrophy gene (DMD) and mitogens induced GTP-binding protein gene (GEM). The expression levels of the three genes in the glaucoma group were significantly lower than those in the normal group. GSEA further illuminated that BMP1, DMD and GEM participated in the occurrence and development of some important metabolic progresses. Using the GSE2378 dataset, we confirmed the high validity of the model, with an area under the receiver operator characteristic curve of 85%.
Conclusion: We identified several key genes, including BMP1, DMD and GEM, that may be involved in the pathogenesis of glaucoma. Our results may help to determine the prognosis of glaucoma and/or to design gene- or molecule-targeted drugs.
Keywords: BMP; DMD; GEM; Gene biomarker; Glaucoma; Prognosis; WGCNA.
©2020 Zhang et al.