Identification of hub genes and pathways of ferroptosis in Fusarium keratitis by bioinformatics methods

Xingbo Teng; Xuewei Xiong; Xiaoyuan Sha; Yahui Lei; Yuyao Diao; Jiayan Liu; Yuan Tian; Lian Liu; Jingxiang Zhong

doi:10.3389/fcimb.2023.1103471

Identification of hub genes and pathways of ferroptosis in Fusarium keratitis by bioinformatics methods

Front Cell Infect Microbiol. 2023 Jan 31:13:1103471. doi: 10.3389/fcimb.2023.1103471. eCollection 2023.

Authors

Xingbo Teng¹, Xuewei Xiong¹, Xiaoyuan Sha¹, Yahui Lei¹, Yuyao Diao¹, Jiayan Liu¹, Yuan Tian¹, Lian Liu¹, Jingxiang Zhong^{1

2}

Affiliations

¹ Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
² The Sixth Affiliated Hospital of Jinan University, Jinan University, Dongguan, China.

Abstract

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.

Keywords: Fusarium keratitis; bioinformatics; ferroptosis; fungal keratitis; immune.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computational Biology
Corneal Ulcer*
Eye Infections, Fungal*
Ferroptosis*
Fusarium* / genetics
Gene Expression Profiling
Keratitis*

Grants and funding

Supported by National Natural Science Foundation of China (Grant number: 81970806, 82271094) and Science and Technology Projects in Guangzhou (Grant number: 202201020030).