Screening and identification of genes related to ferroptosis in keratoconus

Abstract

Abstract Background: Corneal keratoconus (KC) is a dilated corneal disease characterized by a central thinning of the cornea, which protrudes into a conical shape and seriously affects vision. However, due to the complex etiology of keratoconus, it is not yet clear and there is no effective treatment method. Ferroptosis is a novel programmed cell death mechanism related to lipid peroxidation, stress, and amino acid metabolism, playing a crucial role in various diseases. This study aims to explore the relationship between keratoconus and ferroptosis, and provide new insights for the treatment of keratoconus diseases Methods: The corresponding mRNA microarray expression matrix data of KC patients were obtained from GEO database (GEO204791). Weighted co-expression network analysis (WGCNA) and support vector machine recursive feature elimination (SVM-RFE) were selected to screen hub genes. And the hub genes were overlapped with ferroptosis genes (FRGs) from FerrDb. GO and GSEA were performed to analyze differential pathways, ssGSEA was used to determine immune status, and then, feasible drugs were predicted by gene-drug network. At the same time, we predicted the miRNA and IncRNA of hub genes to identify the underlying mechanism of disease and predicted the treatment of disease. Results: The epithelial transcriptome from keratoconus tissue mRNA microarray data (GSE204791) was extracted for the main analysis, including eight epithelial cells (EKC) and eight epithelial control cells (EN). The differential genes that were overlapped by WGCAN, SVM-RFE and FRGs were mainly related to oxidative stress, immune regulation, cellular inflammation and metal ion transport. Aldo-keto reductase family 1 member C3 (AKR1C3) was selected out, through further analysis, and negatively correlated with mature CD56 natural killer (NK) cells and macrophages. And then, gene-drug interaction network analysis and miRNA prediction were performed through the website. At the end, A total of four Immune-related drugs (INDOMETHACIN, DAUNORUBICIN, DOXORUBICIN，DOCETAXEL) and a miRNA (has-miR-184) were screened to predict potential drugs and targets for disease treatment. Conclusion: For the first time , we associated KC with ferroptosis, searched for differential genes to predict the drug targets of gene immunotherapy. Our findings provided a viewpoint and insight for the analysis and treatment of KC.