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Identification of hub genes and pathways of ferroptosis in Fusarium keratitis by bioinformatics methods
Xingbo Teng1, Xuewei Xiong1, Xiaoyuan Sha1
1Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
Background:
Fungal keratitis is a common blinding eye disease, and Fusarium is one of the main species that cause fungal keratitis. As is well known, oxidative stress plays an important role in Fusarium keratitis and it is also a significant initiating factor of ferroptosis. But the relationship between Fusarium keratitis and ferroptosis is currently unclear. This study aimed to speculate and validate potential ferroptosis-related genes in Fusarium keratitis using bioinformatics analysis, which provided ideas for further research on its specific mechanism and new targets for its treatment.
Methods:
The microarray expression profiling dataset (GSE58291) came from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were obtained by the limma package of the R software. The DEGs were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Then, the DEGs were intersected with the genes in the ferroptosis database. The top 5 hub genes were obtained by the protein-protein interaction (PPI) network analysis and the cytoHubba plug-in of Cytoscape software. The hub genes were subjected to GSEA analysis. Then we analyzed the immune infiltration of the samples by CIBERSORT and ssGSEA algorithm. Finally, we validated the mRNA of hub genes by qPCR.
Results:
A total of 1,368 DEGs were identified and 26 ferroptosis-related DEGs were obtained. At the same time, ferroptosis-related pathways were enriched by GO and KEGG using DEGs. HMOX1, CYBB, GPX2, ALOX5 and SRC were obtained by the PPI network analysis and the cytoHubba plug-in of Cytoscape software. The iron metabolism and immune response related pathways were enriched using GSEA. They included hematopoietic cell lineage, lysosome and FC gamma R mediated phagocytosis. T cells follicular helper, monocytes, macrophages and mast cells might play an important role in Fusarium keratitis using analysis of immune infiltration. Finally, qPCR confirmed that the expression of HMOX1, CYBB, ALOX5 mRNA in the DON group was significantly elevated, while the expression of GPX2 were significantly decreased.
Conclusions:
Ferroptosis may play an important role in Fusarium keratitis. HMOX1, CYBB, ALOX5 and GPX2 may be key ferroptosis-related genes in the pathogenesis of Fusarium keratitis.
Insights
This study investigated ferroptosis in Fusarium keratitis, identifying key genes like HMOX1 and CYBB. These findings offer new therapeutic targets for this blinding eye disease.
Area of Science:
- Ophthalmology
- Molecular Biology
- Bioinformatics
Background:
- Fungal keratitis, a leading cause of blindness, is often caused by Fusarium species.
- Oxidative stress is implicated in Fusarium keratitis and is a known trigger for ferroptosis.
- The precise relationship between Fusarium keratitis and ferroptosis remains largely unexplored.
Purpose of the Study:
- To identify and validate potential ferroptosis-related genes involved in Fusarium keratitis.
- To provide insights into the molecular mechanisms and potential therapeutic targets for Fusarium keratitis.
Main Methods:
- Utilized bioinformatics analysis on a microarray dataset (GSE58291) to identify differentially expressed genes (DEGs).
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on DEGs.
- Integrated DEGs with a ferroptosis database and employed protein-protein interaction (PPI) network analysis to identify hub genes.
- Conducted Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis (CIBERSORT, ssGSEA).
- Validated mRNA expression of key genes using quantitative polymerase chain reaction (qPCR).
Main Results:
- Identified 1,368 DEGs, with 26 ferroptosis-related DEGs.
- Enriched ferroptosis-related pathways using GO and KEGG analyses.
- Identified HMOX1, CYBB, GPX2, ALOX5, and SRC as key hub genes via PPI network analysis.
- GSEA revealed enrichment in iron metabolism and immune response pathways, including hematopoietic cell lineage and lysosome.
- Immune infiltration analysis suggested roles for T cells, monocytes, macrophages, and mast cells.
- qPCR confirmed elevated HMOX1, CYBB, and ALOX5 mRNA expression and decreased GPX2 mRNA expression in the DON group.
Conclusions:
- Ferroptosis likely plays a significant role in the pathogenesis of Fusarium keratitis.
- HMOX1, CYBB, ALOX5, and GPX2 are identified as crucial ferroptosis-related genes in Fusarium keratitis.
- These genes represent potential targets for novel therapeutic strategies against fungal keratitis.
