Abstract
Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD), a serious health problem worldwide, can involve ferroptosis. This study aimed to comprehensively analyze the ferroptosis-related genes associated with MAFLD. Methods: Ferroptosis-related differentially expressed genes (FRDEGs) were identified in patients with MAFLD and healthy individuals. Gene ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and gene set enrichment analysis (GSEA) were used to analyze the relevant action pathways of the FRDEGs. The Encyclopedia of RNA Interactomes, CHIPBase, and comparative toxicogenomics databases were used to build mRNA-miRNA, mRNA-transcription factor (TF), and mRNA-drug interaction networks, respectively. A diagnostic model was constructed and bioinformatics analysis methods, such as least absolute shrinkage and selection operator regression analysis, Cox regression analysis, nomogram-based analysis, consensus clustering analysis, and single-sample GSEA, were used to systematically investigate the prognostic values and immunologic characteristics. Results: A total of 13 FRDEGs were obtained and eight were used to construct a diagnostic model and perform a prognostic analysis. Hub genes were also used to construct mRNA-miRNA and mRNA-TF interaction networks and potential drug or molecular compounds. Two MAFLD subtypes were identified: cluster2, which represents an "immunoactive" type, and cluster1, which represents an "immunosuppressive" type; a significant correlation was observed between the immune cell contents and the expression of three FRDEGs (NR4A1, FADS2, and SCD). Conclusion: A ferroptosis-related gene signature was constructed to diagnose MAFLD-associated steatohepatitis, predict the prognosis of MAFLD patients, and analyze the immunologic characteristics of MAFLD. Our findings may provide insights into developing innovative MAFLD treatment techniques.