Consistent Biomarkers and Related Pathogenesis Underlying Asthma Revealed by Systems Biology Approach

Abstract

Asthma is a common chronic airway disease worldwide. Due to its clinical and genetic heterogeneity, the cellular and molecular processes in asthma are highly complex and relatively unknown. To discover novel biomarkers and the molecular mechanisms underlying asthma, several studies have been conducted by focusing on gene expression patterns in epithelium through microarray analysis. However, few robust specific biomarkers were identified and some inconsistent results were observed. Therefore, it is imperative to conduct a robust analysis to solve these problems. Herein, an integrated gene expression analysis of ten independent, publicly available microarray data of bronchial epithelial cells from 348 asthmatic patients and 208 healthy controls was performed. As a result, 78 up- and 75 down-regulated genes were identified in bronchial epithelium of asthmatics. Comprehensive functional enrichment and pathway analysis revealed that response to chemical stimulus, extracellular region, pathways in cancer, and arachidonic acid metabolism were the four most significantly enriched terms. In the protein-protein interaction network, three main communities associated with cytoskeleton, response to lipid, and regulation of response to stimulus were established, and the most highly ranked 6 hub genes (up-regulated CD44, KRT6A, CEACAM5, SERPINB2, and down-regulated LTF and MUC5B) were identified and should be considered as new biomarkers. Pathway cross-talk analysis highlights that signaling pathways mediated by IL-4/13 and transcription factor HIF-1α and FOXA1 play crucial roles in the pathogenesis of asthma. Interestingly, three chemicals, polyphenol catechin, antibiotic lomefloxacin, and natural alkaloid boldine, were predicted and may be potential drugs for asthma treatment. Taken together, our findings shed new light on the common molecular pathogenesis mechanisms of asthma and provide theoretical support for further clinical therapeutic studies.

Transcriptomic analysis delineates potential signature genes and miRNAs associated with the pathogenesis of asthma

“…Lactoferrin or lactotransferrin (LTF) serves as an anti-inflammatory factor and an immunomodulator. LTF which is an iron-binding glycoprotein has been shown upregulated during asthma development in our study as also reported by other studies 26 , 27 . A report by Lourdes Fernández-Delgado et al .…”

“…Lactoferrin or lactotransferrin (LTF) serves as an anti-inflammatory factor and an immunomodulator. LTF which is an iron-binding glycoprotein has been shown upregulated during asthma development in our study as also reported by other studies 26,27 . A report by Lourdes Fernández-Delgado et al suggested a new mechanism of LTF release by human neutrophils on activation by galectin-3 and claimed the pro-inflammatory role of LTF in allergic asthma 28 .…”

<p>Identification of Transcriptional Metabolic Dysregulation in Subtypes of Pituitary Adenoma by Integrated Bioinformatics Analysis</p>

“…To determine the changed tendency of pathways in tumors, the Z-score was calculated in each term using the following formula:19,20…”

Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome

“…Mounting evidence shows that metabolic syndrome and insulin resistance are associated with worsened outcomes of chronic lung disease [ 91 ], as well as microbiome dysbiosis notably in the airways of patients with asthma [ 92 ]. Boldine is predicted to be potential drug for asthma treatment [ 93 ]. Nuciferine can induce relaxation in contracted tracheal rings.…”