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bioRxiv · 10.1101/2025.02.26.639889

Validation of bronchial airway gene expression associated with bronchiectasis in nasal epithelium

Souery, W.·Wong, J.·Diaz, A. A.·Xu, K.·Xiao, X.·Liu, H.·Liu, G.·Gower, A. C.·Alekseyev, Y.·Billatos, E.·Lenburg, M. E.
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Abstract

ObjectivesExamination of bronchial epithelium-derived gene expression signature of bronchiectasis (BE) in nasal epithelium. MethodsWe studied 220 participants from the Detection of Early Lung Cancer Among Military Personnel study with bulk RNA-seq of nasal epithelium brushings. Gene set enrichment analysis (GSEA) was used to examine whether genes previously identified as increased or decreased in the bronchial epithelium of individuals with radiologic BE are significantly enriched among the genes most significantly altered in the nasal epithelium. GSEA and cell-type specific gene expression signatures were used to examine changes in the cellular composition of nasal epithelium associated with radiologic BE. ResultsGenes previously found to have significantly altered expression in bronchial epithelium in radiologic BE are concordantly enriched among the genes most increased or decreased in nasal epithelium in radiologic BE in this validation set (p = 3x10-7, increased; p = 6x10-8, decreased). GSEA performed using cell-type signatures demonstrates that in nasal epithelium, BE is associated with increased multiciliated and deuterosomal cell-related gene expression and decreased expression of basal cell- related gene expression, consistent with our previous findings in bronchial epithelium. ConclusionOur work validates our bronchial signature of BE in an independent dataset and demonstrates that similar gene expression changes are associated with radiologic BE in the bronchial and nasal epithelium. These findings support considering nasal epithelium brushing as a less invasive tool for screening and monitoring BE. SummaryThis study validates a previously reported bronchial signature of bronchiectasis (BE) in nasal epithelium. Changes in gene expression and cell-type composition associated with radiologic BE are similar across both bronchial and nasal epithelium.

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Souery, W., Wong, J., Diaz, A. A., Xu, K., Xiao, X., Liu, H., Liu, G., Gower, A. C., Alekseyev, Y., Billatos, E., Lenburg, M. E.. 2025-02-28. Validation of bronchial airway gene expression associated with bronchiectasis in nasal epithelium. https://doi.org/10.1101/2025.02.26.639889

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