International ophthalmology · 2024
Identification of hub genes and molecular pathways in keratoconus by integrating bioinformatics and literature mining at the RNA level.
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Meng Feiying, Ren Shengwei
Аннотация
OBJECTIVE: Keratoconus (KC) is a condition characterized by progressive corneal steepening and thinning. However, its pathophysiological mechanism remains vague. We mainly performed literature mining to extract bioinformatic and related data on KC at the RNA level. The objective of this study was to explore the potential pathological mechanisms of KC by identifying hub genes and key molecular pathways at the RNA level.
METHODS: We performed an exhaustive search of the PubMed database and identified studies that pertained to gene transcripts derived from diverse corneal layers in patients with KC. The identified differentially expressed genes were intersected, and overlapping genes were extracted for further analyses. Significantly enriched genes were screened using "Gene Ontology" (GO) and "Kyoto Encyclopedia of Genes and Genomes" (KEGG) analysis with the "Database for Annotation, Visualization, and Integrated Discovery" (DAVID) database. A protein-protein interaction (PPI) network was constructed for the significantly enriched genes using the STRING database. The PPI network was visualized using the Cytoscape software, and hub genes were screened via betweenness centrality values. Pathways that play a critical role in the pathophysiology of KC were discovered using the GO and KEGG analyses of the hub genes.
RESULTS: 68 overlapping genes were obtained. Fifty genes were significantly enriched in 67 biological processes, and 16 genes were identified in 7 KEGG pathways. Moreover, 14 nodes and 32 edges were identified via the PPI network constructed using the STRING database. Multiple analyses identified 4 hub genes, 12 enriched biological processes, and 6 KEGG pathways. GO enrichment analysis showed that the hub genes are mainly involved in the positive regulation of apoptotic process, and KEGG analysis showed that the hub genes are primarily associated with the interleukin-17 (IL-17) and tumor necrosis factor (TNF) pathways. Overall, the matrix metalloproteinase 9, IL-6, estrogen receptor 1, and prostaglandin-endoperoxide synthase 2 were the potential important genes associated with KC.
CONCLUSION: Four genes, matrix metalloproteinase 9, IL-6, estrogen receptor 1, and prostaglandin endoperoxide synthase 2, as well as IL-17 and TNF pathways, are critical in the development of KC. Inflammation and apoptosis may contribute to the pathogenesis of KC.
METHODS: We performed an exhaustive search of the PubMed database and identified studies that pertained to gene transcripts derived from diverse corneal layers in patients with KC. The identified differentially expressed genes were intersected, and overlapping genes were extracted for further analyses. Significantly enriched genes were screened using "Gene Ontology" (GO) and "Kyoto Encyclopedia of Genes and Genomes" (KEGG) analysis with the "Database for Annotation, Visualization, and Integrated Discovery" (DAVID) database. A protein-protein interaction (PPI) network was constructed for the significantly enriched genes using the STRING database. The PPI network was visualized using the Cytoscape software, and hub genes were screened via betweenness centrality values. Pathways that play a critical role in the pathophysiology of KC were discovered using the GO and KEGG analyses of the hub genes.
RESULTS: 68 overlapping genes were obtained. Fifty genes were significantly enriched in 67 biological processes, and 16 genes were identified in 7 KEGG pathways. Moreover, 14 nodes and 32 edges were identified via the PPI network constructed using the STRING database. Multiple analyses identified 4 hub genes, 12 enriched biological processes, and 6 KEGG pathways. GO enrichment analysis showed that the hub genes are mainly involved in the positive regulation of apoptotic process, and KEGG analysis showed that the hub genes are primarily associated with the interleukin-17 (IL-17) and tumor necrosis factor (TNF) pathways. Overall, the matrix metalloproteinase 9, IL-6, estrogen receptor 1, and prostaglandin-endoperoxide synthase 2 were the potential important genes associated with KC.
CONCLUSION: Four genes, matrix metalloproteinase 9, IL-6, estrogen receptor 1, and prostaglandin endoperoxide synthase 2, as well as IL-17 and TNF pathways, are critical in the development of KC. Inflammation and apoptosis may contribute to the pathogenesis of KC.