Identifying a biomarker network for corticosteroid resistance in asthma from bronchoalveolar lavage samples

详细信息    查看全文

• 作者：José Eduardo Vargas ; Bárbara Nery Porto ; Renato Puga…
• 刊名：Molecular Biology Reports
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：43
• 期：7
• 页码：697-710
• 全文大小：1,383 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Animal Anatomy, Morphology and Histology
  Animal Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-4978
• 卷排序：43

文摘

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.KeywordsSevere asthmaCorticosteroid resistanceSystems biologyBiomarker network