Molecular markers of pediatric cholesteatoma: A gene expression comparison with adult tissue

OBJECTIVE: This study aims to compare gene expression levels in pediatric versus adult cholesteatoma using bulk RNA sequencing. STUDY DESIGN: Retrospective analysis of prospectively collected human tissue. SETTING: Tertiary medical center. METHODS: RNA sequencing was performed on 3 pediatric and 3 adult cholesteatoma tissue samples and differentially expressed genes were identified. Gene set enrichment analysis (GSEA) was performed to identify mechanistic pathways and differential cellular reprogramming. RESULTS: Bulk RNA sequencing of 3 pediatric and 3 adult cholesteatoma tissue samples identified 20,298 genes. Differential gene expression analysis revealed 14 genes: 6 downregulated in and 8 upregulated in pediatric cholesteatoma compared to adult tissue. The GSEA revealed 3 gene sets upregulated in pediatric samples compared to adults relevant in cholesteatoma literature: Tumor Necrosis Factor (TNF-α), Transforming Growth Factor Beta (TGF-β, and the Epithelial-Mesenchymal Transition (EMT). CONCLUSION: Pediatric cholesteatoma has distinct gene expression and pathway enrichment compared to adult disease, involving inflammation and fibrosis. This study highlights the complex inflammatory process seen in pediatric cholesteatoma and suggests molecular markers that could serve as potential therapeutic targets for treatment.