[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma]

Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.