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Distinct and Shared Molecular Mechanisms in Pediatric Antrochoanal Polyps and Chronic Rhinosinusitis with Nasal
Yong-Chao Chen1, Xin Wang1, Yan-Wen Pan1
1Department of Otorhinolaryngology, Shenzhen Children's Hospital, Shenzhen, Guangdong, People's Republic of China.
Insights
Pediatric antrochoanal polyps (ACP) show oxidative stress and lipid changes, while chronic rhinosinusitis with nasal polyps (CRSwNP) involves immune and ciliary dysfunction. Both share inflammation, with distinct tryptophan metabolism pathways.
Area of Science:
- Otorhinolaryngology
- Proteomics
- Metabolomics
- Pediatric diseases
Background:
- Mechanisms of pediatric antrochoanal polyps (ACP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are poorly understood.
- This study aims to elucidate the distinct and overlapping molecular pathways involved in these pediatric nasal conditions.
Purpose of the Study:
- To investigate the proteomic and metabolomic profiles of pediatric ACP and CRSwNP.
- To identify unique and shared molecular pathways contributing to the pathogenesis of these conditions.
Main Methods:
- Proteomic and non-targeted metabolomic analyses were performed on nasal polyp tissues from children with ACP, CRSwNP, and healthy controls.
- Data-independent acquisition (DIA) mass spectrometry and UPLC-MS/MS were utilized for protein and metabolite profiling.
- Integrated pathway analysis was employed to explore the functional roles of identified molecular differences.
Main Results:
- Proteomic analysis revealed differentially expressed proteins (DEPs) in both ACP (1000 DEPs) and CRSwNP (880 DEPs) compared to controls, with key proteins like PEX1 and LYPD2 in ACP, and PEX1, CFAP52, SPAG6, and DHRS9 in CRSwNP.
- Metabolomic analysis identified 129 differential metabolites in ACP and 11 in CRSwNP, notably showing opposite regulation of 5-HTP between the two conditions.
- Pathway analysis indicated oxidative stress and lipid metabolism disruptions in ACP, and immune and ciliary dysfunction in CRSwNP, with shared inflammation and extracellular matrix remodeling.
Conclusions:
- Pediatric ACP is characterized by oxidative stress and lipid dysregulation, distinct from the ciliary and immune dysfunction observed in CRSwNP.
- Shared features include inflammation and extracellular matrix remodeling, while tryptophan metabolism, specifically 5-HTP levels, differs significantly.
- Proteins such as PEX1, LYPD2, CFAP52, and 5-HTP represent potential biomarkers for improved diagnosis and targeted therapies, though further validation in larger cohorts is necessary.
Purpose:
The underlying mechanisms of pediatric antrochoanal polyps (ACP)and chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely unexplored. This study investigates their proteomic and metabolomic profiles to uncover unique and overlapping pathways, shedding light on their underlying causes.
Methods:
Specimens were collected from six children with ACP, six with CRSwNP, and six with normal inferior turbinate mucosa (CK) at Shenzhen Children's Hospital. Protein profiles were analyzed using data-independent acquisition (DIA) mass spectrometry, while metabolite profiles were assessed via non-targeted metabolomics (UPLC-MS/MS). Differences in proteins and metabolites were identified through statistical selection and bioinformatics, followed by integrated pathway analysis to explore their roles in disease processes.
Results:
Proteomic analysis identified 1000 differentially expressed proteins (DEPs) in ACP and 880 in CRSwNP compared to controls. Key DEPs in ACP included PEX1 and LYPD2, while CRSwNP included PEX1, CFAP52, SPAG6 and DHRS9. Metabolomic analysis identified 129 differential metabolites in ACP and 11 in CRSwNP, with 5-HTP showing opposite regulation between the two conditions. Pathway analysis pointed to oxidative stress and lipid metabolism disruptions in ACP, and immune and ciliary dysfunction in CRSwNP. Both conditions shared inflammation and extracellular matrix remodeling, but tryptophan metabolism diverged, with 5-HTP reduced in ACP and elevated in CRSwNP.
Conclusion:
This study highlights oxidative stress and lipid dysregulation as hallmarks of pediatric ACP, distinct from ciliary and immune dysfunction in CRSwNP, with inflammation and matrix remodeling as common features. The opposing regulation of 5-HTP reflects differences in tryptophan metabolism. Key molecules like PEX1, LYPD2, CFAP52, and 5-HTP emerge as potential biomarkers, offering promise for improved diagnosis and targeted therapies in nasal polyp-related conditions, but the small sample size and exploratory design require validation in larger cohorts to ensure clinical applicability.
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