title: Identifying a biomarker network for corticosteroid resistance in asthma from bronchoalveolar lavage samples.
abstract: Corticosteroid resistance (CR) is a major barrier to the effective treatment of severe asthma. Hence, a better understanding of the molecular mechanisms involved in this condition is a priority. Network analysis is an emerging strategy to explore this complex heterogeneous disorder at system level to identify a small own network for CR in asthma. Gene expression profile of GSE7368 from bronchoalveolar lavage (BAL) of CR in subjects with asthma was downloaded from the gene expression omnibus (GEO) database and compared to BAL of corticosteroid-sensitive (CS) patients. DEGs were identified by the Limma package in R language. In addition, DEGs were mapped to STRING to acquire protein-protein interaction (PPI) pairs. Topological properties of PPI network were calculated by Centiscape, ClusterOne and BINGO. Subsequently, text-mining tools were applied to design one own cell signalling for CR in asthma. Thirty-five PPI networks were obtained; including a major network consisted of 370 nodes, connected by 777 edges. After topological analysis, a minor PPI network composed by 48 nodes was indentified, which is composed by most relevant nodes of major PPI network. In this subnetwork, several receptors (EGFR, EGR1, ESR2, PGR), transcription factors (MYC, JAK), cytokines (IL8, IL6, IL1B), one chemokine (CXCL1), one kinase (SRC) and one cyclooxygenase (PTGS2) were described to be associated with inflammatory environment and steroid resistance in asthma. We suggest a biomarker network composed by 48 nodes that could be potentially explored with diagnostic or therapeutic use.
authors.affiliation: Centro Infant - Pontifical Catholic University of Rio Grande do Sul - PUCRS, Av. Ipiranga, 6681, Porto Alegre, RS, 91501-970, Brazil. josevargas123@gmail.com.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Vargas
authors.affiliation: Centro Infant - Pontifical Catholic University of Rio Grande do Sul - PUCRS, Av. Ipiranga, 6681, Porto Alegre, RS, 91501-970, Brazil.
authors.forename: Bárbara Nery
authors.initials: BN
authors.lastname: Porto
authors.affiliation: Clinical Research Center, Hospital Israelita Albert Einstein- HIAE, São Paulo, Brazil.
authors.forename: Renato
authors.initials: R
authors.lastname: Puga
authors.affiliation: Centro Infant - Pontifical Catholic University of Rio Grande do Sul - PUCRS, Av. Ipiranga, 6681, Porto Alegre, RS, 91501-970, Brazil.
authors.forename: Renato Tetelbom
authors.initials: RT
authors.lastname: Stein
authors.affiliation: Centro Infant - Pontifical Catholic University of Rio Grande do Sul - PUCRS, Av. Ipiranga, 6681, Porto Alegre, RS, 91501-970, Brazil.
authors.forename: Paulo Márcio
authors.initials: PM
authors.lastname: Pitrez
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D004361:Drug Tolerance; D063990:Gene Ontology; D006801:Humans; D060066:Protein Interaction Maps; D015398:Signal Transduction
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D015415:Biomarkers
keywords: Biomarker network; Corticosteroid resistance; Severe asthma; Systems biology