Exploration of Key Markers Driving Ferroptosis in the Progression of Non-Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition strongly linked to obesity, diabetes, and metabolic syndrome. Its global incidence is steadily increasing, placing a significant health burden on both patients and society. Despite existing treatments, such as lifestyle changes and medications, the lack of effective biomarkers and therapeutic strategies leaves many patients at risk for disease progression. This study aims to identify ferroptosis-related differentially expressed genes (DEGs) through bioinformatics analysis and to explore their roles in NAFLD. By comparing samples from NAFLD patients and healthy controls, we identified 1,770 significant DEGs, with 1,073 being upregulated and 697 downregulated. Pathway analysis revealed a marked decrease in expression within certain key metabolic pathways (such as the one-carbon pool by folate) in the NAFLD group, while expression in DNA repair-related pathways (such as non-homologous end joining) was significantly increased. Additionally, immune cell infiltration analysis showed significant differences in 19 immune cell types between the NAFLD and control groups, with 12 types exhibiting increased infiltration in the NAFLD group. Through protein-protein interaction (PPI) network analysis, we identified 41 critical intersecting genes, and ROC curve validation demonstrated that 25 of these genes had an AUC value exceeding 0.85, highlighting their potential as biomarkers for NAFLD. In conclusion, this study sheds light on the underlying molecular mechanisms of NAFLD and identifies promising genes as potential biomarkers, providing a crucial foundation for future early diagnosis and personalized treatment. Competing Interest Statement The authors have declared no competing interest. Clinical Trial "N/A" Funding Statement Yes Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Exempted - Data is from public database I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All relevant data are within the manuscript and its Supporting Information files.