Gene signatures from U-BIOPRED transcriptomic-associated clusters exist in COPD
EUROPEAN RESPIRATORY JOURNAL(2017)
摘要
Background: Severe asthma and COPD share pathophysiologic traits such as chronic airflow obstruction, exacerbations and corticosteroid insensitivity. Aim: To examine whether there are common mechanisms through a molecular approach. Methods: Three transcriptomic-associated clusters (TACs) were described from a hierarchical analysis of sputum transcriptomics of U-BIOPRED cohort: TAC1=High T-2; TAC2= inflammasome; TAC3= Mitochondrial OXPHOS [Kuo at al. Eur Respir J.2017, 49, in press]. Using gene set variation analysis (GSVA), we examined the distribution of the 3 TACs in the transcriptome of bronchial biopsies from the GLUCOLD cohort (GSE36221). Results: Bronchial biopsies at baseline showed a wide range of expression of the 3 TACs, with a significant inverse correlation between ES TAC3 and ES TAC1 but a positive correlation between TAC3 and TAC2. After combined inhaled corticosteroids (ICS) and LABA, ES of TAC1 was significantly reduced at 6 and 30 months, but TAC2 and TAC3 ES were not affected. Conclusions: Mitochondrial dysfunction is present in COPD as previously reported, and that the expression of the 3 asthma-derived TACs in COPD indicate potential overlap of molecular pathways. As predicted, TAC1 is the only signature suppressed by ICS. Severe asthma and COPD may share common pathways.
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