Gene expression profile of human lung in a relatively early stage of COPD with emphysema

Abstract

Ina Jeong,1,* Jae-Hyun Lim,2,* Dong Kyu Oh,3 Woo Jin Kim,4 Yeon-Mok Oh3 1Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea; 2Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea *These authors contributed equally to this work Purpose: As only some smokers develop COPD with emphysema, we explored the molecular pathogenesis of early-stage COPD with emphysema using gene expression profiling of human lung tissues. Patients and methods: First, 110 subjects who had smoked more than ten pack-years were classified into three groups: COPD with emphysema, COPD without emphysema, and healthy smokers. COPD and emphysema were confirmed by post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.7 and by chest computed tomography. Lung tissues obtained surgically from the 110 subjects were processed and used for RNA-Seq analysis. Results: Among the 110 subjects, 29 had COPD with emphysema, 21 had COPD without emphysema, and 60 were healthy smokers; their mean post-bronchodilator forced expiratory volume in 1 second values were 78%, 80%, and 94%, respectively. Using RNA-Seq, we evaluated 16,676 genes expressed in lung tissues. Among them, 1,226 genes in the COPD with emphysema group and 434 genes in the COPD without emphysema group were differentially expressed genes compared to the expression in healthy smokers. In the COPD with emphysema group, ACER2 and LMAN2L were markedly increased and decreased, respectively. In the COPD without emphysema group, the CHRM3 gene, previously reported to be associated with COPD, and HDAC10 were markedly increased and decreased, respectively. Conclusion: Our study identified differences in gene expression in subjects with COPD according to emphysema status using RNA-Seq transcriptome analysis. These findings may have mechanistic implications in COPD. Keywords: COPD, emphysema, RNA-Seq, transcriptome, gene

Keywords

• COPD
• emphysema
• RNA-Seq
• transcriptome
• gene