The Role of Ferroptosis in Adenoid Hypertrophy in Children with Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea (OSA) is a common sleep disorder in children, with adenoid hypertrophy was recognized as the main cause. While ferroptosis has been linked to adult OSA, its role in children with adenoid hypertrophy remains unclear. Here, we aimed to explore the potential role of ferroptosis in pediatric OSA-associated adenoid hypertrophy.

We conducted RNA sequencing on adenoid tissues from children with OSA stratified by severity (mild-to-moderate, n=9; severe, n=9). Hub genes were identified by integrating differentially expressed genes (DEGs) with ferroptosis-related genes and constructing a protein-protein interaction (PPI) network. We further validated these findings in an independent cohort and primary cells.

KEGG enrichment analysis revealed significant alterations in ferroptosis-related pathways, including p53 signaling pathway and Glutathione metabolism (p < 0.05). We identified 108 ferroptosis-related DEGs (fold change: 0.45-6.42, adjusted p < 0.05) and subsequently pinpointed 8 hub genes through PPI network construction and Cytoscape analysis (fold change:0.61-1.81, adjusted p < 0.05). In clinical sample validation, mild-to-moderate tissues exhibited significant activation of ferroptosis. With the exception of PLA2G7, the expression trends of the other 7 hub DEGs were consistent with the findings from bioinformatics analysis. Moreover, ferroptosis inducers significantly suppressed the proliferation of adenoid primary cells in vitro (inhibition rate ≈70%, p < 0.0001).

This study helps us better understand how ferroptosis contributes to adenoid hypertrophy in children with OSA and also suggests that ferroptosis activation may attenuate disease advancement. Furthermore, the 7 hub genes are proposed as potential biomarkers and drug-binding targets.