ITGAM and FCGR3B contribute to recurrent and limited CRSwNP in children through phagosome pathway
1Department of Otolaryngology, Head and Neck Surgery, Beijing Childrens Hospital, Capital Medical University, National Center for Childrens Health, Beijing, China.
Background:
Chronic rhinosinusitis with nasal polyps (CRSwNP) is more common in children with limited CRSwNP (L-CRSwNP). L-CRSwNP shares similar clinical phenotypes with recurrent CRSwNP (R-CRSwNP). This study aimed to explore the molecular mechanisms of L- and R-CRSwNP in children.
Methodology:
Compared clinical characteristics and RNA sequencing data of 20 L-CRSwNP and 5 R-CRSwNP in children. Paired analyzed RNA sequencing data of 6 children with L-CRSwNP polyps and mucosal tissue samples. Conducted GO and KEGG enrichment analyses. Identified hub genes through protein-protein interaction networks (PPI). Validated hub genes in L- and R-CRSwNP using real-time quantitative PCR (RT-qPCR), immunohistochemistry (IHC), and multiplex immunohistochemistry (mIHC).
Results:
RNA-seq analysis of L- and R-CRSwNP polyp showed no differentially expressed genes (DEGs). RNA-seq paired analysis of L-CRSwNP identified 1419 DEGs. GO enrichment analysis showed significant enrichment for biological processes associated with neutrophils. ITGAM and FCGR3B were identified as hub genes by PPI analysis. RT-qPCR and IHC results suggested the expression levels of ITGAM and FCGR3B were significantly increased in L- and R-CRSwNP. mIHC results suggested ITGAM and FCGR3B were closely associated with neutrophils and M2 macrophages in L- and R-CRSwNP.
Conclusions:
L- and R-CRSwNP in children exhibit similar clinical phenotypes and molecular mechanisms. ITGAM and FCGR3B are hub genes contributing to disease through neutrophil- and M2 macrophage-mediated phagosome pathway.
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