Identification of ferroptosis-related genes in pediatric Crohn's disease using bioinformatics approaches
Peng Lin1, Shuxia Xu2, Xiaoxiao Yan1
1Department of Pathology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, China.
Insights
Ferroptosis plays a key role in pediatric Crohn's disease (PCD). This study identified key ferroptosis genes and immune cells, revealing IL1B as a promising diagnostic marker for PCD.
Area of Science:
- Biomedical research
- Genomics
- Immunology
Background:
- Ferroptosis is a critical mechanism in inflammatory bowel disease (IBD).
- Understanding ferroptosis in pediatric Crohn's disease (PCD) is crucial for targeted therapies.
Purpose of the Study:
- Identify key ferroptosis-related genes (FRGs) in PCD.
- Analyze dysregulated signaling pathways and immune infiltration in PCD.
- Evaluate diagnostic potential of identified genes.
Main Methods:
- Integrated bioinformatics analysis of gene expression data (GSE117993).
- Ferroptosis-related gene (FRG) curation from FerrDb.
- Protein-protein interaction (PPI) network analysis.
- Immune cell infiltration assessment (ssGSEA).
- Receiver operating characteristic (ROC) curve analysis for validation.
Main Results:
- Identified 1,074 differentially expressed genes (DEGs), including 21 FRGs-DEGs.
- Enrichment analysis linked FRGs-DEGs to metabolic regulation and IL-17 signaling.
- Five hub genes identified: PTGS2, IFNG, IL1B, IDO1, NOS2.
- Significant accumulation of myeloid-derived suppressor cells (MDSCs) and neutrophils observed.
- IL1B showed the highest diagnostic performance in validation cohorts.
Conclusions:
- This study provides novel insights into ferroptosis mechanisms in PCD.
- Identified hub genes, particularly IL1B, serve as potential diagnostic biomarkers.
- Findings support advancing precision therapy for pediatric Crohn's disease.
Abstract:
Ferroptosis is increasingly implicated as a critical pathogenic mechanism in inflammatory bowel disease (IBD). This study employed integrated bioinformatics approaches to identify key ferroptosis-related genes (FRGs), dysregulated signaling pathways, and immune infiltration patterns in pediatric Crohn's disease (PCD). Gene expression profiles from the GSE117993 dataset (92 PCD patients, 55 healthy controls) were analyzed to identify differentially expressed genes (DEGs). FRGs were curated from the FerrDb database. Intersection analysis revealed FRGs-DEGs, which underwent functional enrichment analysis. Protein-protein interaction (PPI) network analysis using CytoHubba identified hub genes. Immune cell infiltration was assessed via single-sample gene set enrichment analysis (ssGSEA). The diagnostic potential of hub genes was evaluated using receiver operating characteristic (ROC) curve analysis in two independent validation cohorts (GSE126124, GSE62207). Bioinformatics analysis identified 1,074 DEGs, including 21 FRGs-DEGs. Enrichment analysis implicated these FRGs-DEGs in metabolic regulation and IL-17 signaling pathway. PPI analysis identified five hub genes: PTGS2, IFNG, IL1B, IDO1, and NOS2. ssGSEA revealed significant accumulation of myeloid-derived suppressor cells (MDSCs) and neutrophils in PCD. Validation results confirmed that all hub genes were significantly differentially expressed (p < 0.01), with IL1B exhibiting the best diagnostic performance. This study reveals promising molecular targets and mechanistic insights to advance PCD diagnosis and precision therapy.
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