Bioinformatics Analysis and Identification of Underlying Biomarkers Potentially Linking Allergic Rhinitis and Asthma

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Abstract
BACKGROUND Rhinitis is the most common clinical manifestation of allergy, affecting more than 400 million people around the world. Rhinitis increases the risk of developing bronchial hyper-responsiveness and asthma. Previous studies have shown that rhinitis is closely related with the physiology, pathology, and pathogenesis of asthma. We analyzed co-expressed genes to explore the relationships between rhinitis and asthma and to find biomarkers of comorbid rhinitis and asthma. MATERIAL AND METHODS Asthma- and rhinitis-related differentially-expressed genes (DEGs) were identified by bioinformatic analysis of GSE104468 and GSE46171 datasets from the Gene Expression Omnibus (GEO) database. After assessment of Gene Ontology (GO) terms and pathway enrichment for DEGs, a protein-protein interaction (PPI) network was conducted via comprehensive target prediction and network analyses. We also evaluated co-expressed DEGs and corresponding predicted miRNAs involved in the developing process of rhinitis and asthma. RESULTS We identified 687 and 1001 DEGs in bronchial and nasal epithelia samples of asthma patients, respectively. For patients with rhinitis, we found 245 DEGs. The hub-genes of PAX6, NMU, NTS, NMUR1, PMCH, and KRT6A may be associated with rhinitis, while CPA3, CTSG, POSTN, CLCA1, HDC, and MUC5B may be involved in asthma. The co-expressed DEGs of BPIFA1, CCL26, CPA3, and CST1, together with corresponding predicted miRNAs (e.g., miR-195-5p and miR-125a-3p) were found to be significantly correlated with rhinitis and asthma. CONCLUSIONS Rhinitis and asthma are related, and there are significant correlations of BPIFA1, CCL26, CPA3, and CST1 genes with novel biomarkers involved in the comorbidity of rhinitis and asthma.

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