Unveiling Ferroptosis-Driven Mechanisms in Liver Fibrosis: A Bioinformatics Approach to Identify Novel Therapeutic Targets.

OBJECTIVE: To explore the potential biological significance and diagnostic value of ferroptosis-related differentially expressed genes (DEGs) in liver fibrosis (LF). STUDY DESIGN: Bioinformatic analysis of a publicly available microarray dataset. Place and Duration of the Study: Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, West Lake University School of Medicine, Hangzhou, China, from June 2 to July 2, 2024. METHODOLOGY: Gene expression data from GSE139602 and ferroptosis-related genes from the GeneCards database were analysed to identify ferroptosis-related DEGs in LF. Functional enrichment, gene set enrichment, immune infiltration, protein-protein interaction, and ROC analyses were performed to identify key genes and their potential roles in LF. RESULTS: Forty-one DEGs were associated with ferroptosis, and LF were identified. Among these, CEBPA, MYC, SCD, and SREBF1 were highlighted as important genes with significant diagnostic ability, confirmed through the receiver operating characteristic curve. Notably, CEBPA and SCD were implicated in fibrosis progression via their roles in lipid metabolism and oxidative stress modulation, which are essential components of ferroptosis. CONCLUSION: The bioinformatics analysis identified four key ferroptosis-related genes-CEBPA, MYC, SCD, and SREBF1-as diagnostic biomarkers for LF. This study found the ferroptosis-related pathways as potential therapeutic targets for LF. KEY WORDS: Biomedicine, Liver fibrosis, Ferroptosis, Differentially expressed genes.