Identification and validation of oxidative stress-related genes in biliary atresia.

Abstract

PURPOSE: Increasing evidence has indicated a role of oxidative stress in the pathogenesis of biliary atresia (BA). This study aimed to identify key oxidative stress-related biomarkers in BA and explore their therapeutic potential. METHODS: BA datasets were obtained from the GEO database. Differentially expressed genes (DEGs) were identified using the GSE46960 dataset. These DEGs were intersected with oxidative stress-related genes from GeneCards to obtain the oxidative stress-related DEGs (ORDEGs). Functional enrichment (GO, KEGG) and gene set enrichment analyses were performed. Hub genes were identified using machine learning and protein-protein interaction (PPI) network analysis. Their expression was validated via qRT-PCR in BA patient liver samples and rhesus rotavirus (RRV)-induced mouse models. Potential transcription factors (TFs), microRNAs, and drugs targeting hub ORDEGs were predicted using TRRUST, TarBase, and DSigDB, respectively. RESULTS: Six hub ORDEGs (CCL2, CXCL8, SPP1, EDN1, TGFB3, and F3) were ultimately identified. Their mRNA levels were significantly upregulated in both BA patients and mice. A total of 52 TFs and 13 microRNAs were identified. Among the predicted drugs, simvastatin may hold therapeutic potential. CONCLUSION: This study identified six key ORDEGs (CCL2, CXCL8, SPP1, EDN1, TGFB3, and F3) to be important pathogenic factors and potential therapeutic targets in BA.