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Integrated transcriptomic and co-expression network analysis identifies HIF1A as a key immune regulator in biliary
Chu Wang1, Lijing Xiong1, Yang Li1
1Department of Pediatric Gastroenterology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Translational Pediatrics
|January 8, 2026
Summary
Hypoxia-inducible factor 1-alpha (HIF1A) is crucial in biliary atresia (BA) pathogenesis, linking hypoxia to immune and fibrotic responses. Targeting HIF1A pathways may offer new avenues for early BA diagnosis and treatment.
Area of Science:
- Neonatal cholestatic liver diseases
- Molecular mechanisms of pediatric liver diseases
- Transcriptomic analysis in developmental disorders
Background:
- Biliary atresia (BA) is a neonatal cholangiopathy with unknown causes.
- Understanding BA's molecular basis is key for diagnosis and therapy.
Purpose of the Study:
- Elucidate BA's molecular mechanisms and regulatory networks.
- Identify key genes and pathways involved in BA pathogenesis.
- Provide insights for early BA diagnosis and targeted treatment.
Main Methods:
- Integrative transcriptomic analysis of three BA liver microarray datasets (GSE46960, GSE15235, GSE159720).
- Identification of differentially expressed genes (DEGs) and functional enrichment analysis (GO, KEGG).
- Immune infiltration analysis, gene-set intersection with developmental pathways (Hedgehog, NOTCH), and Weighted Gene Co-expression Network Analysis (WGCNA).
Main Results:
- Identified 343 DEGs in BA, enriched in immune activation, cytokine signaling, and fibrosis pathways.
- Hypoxia-inducible factor 1-alpha (HIF1A) was consistently upregulated and associated with immune cell infiltration (neutrophils, monocytes, T cells).
- HIF1A-stratified DEGs revealed enrichment in inflammatory, hypoxia-signaling, and bile acid transport pathways; WGCNA identified a HIF1A-correlated module linked to leukocyte chemotaxis.
Conclusions:
- HIF1A plays a central role in BA pathogenesis by connecting hypoxia to immune and fibrotic remodeling.
- HIF1A and its downstream networks are potential targets for early BA detection and intervention.
- Further validation in larger cohorts and experimental models is warranted.
