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

Abstract

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

Supplementary materials

Figure S1 Schematic overview of the transcript analysis of the RNA-seq experiment.

Notes: Briefly, we used TopHat to align raw FASTQ files and used Cufflinks read annotation and quantification. FastQC was used to check read quality.

Abbreviation: FPKM, fragments per kilobase of exon per million fragments mapped.

Figure S2 Schematic Venn diagram of the number of DEGs in the three subjects groups.

Notes: In the COPD with emphysema group, 1,588 genes were upregulated and 1,519 genes were downregulated, compared with those in healthy smokers. In the COPD without emphysema group, 1,257 genes were upregulated and 1,058 genes were downregulated, compared with those in healthy smokers. In both COPD groups, 939 genes were upregulated and 942 genes were downregulated, compared with those in healthy smokers.

Abbreviation: DEGs, differentially expressed genes.

Acknowledgments

This work was supported by the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant number HC16C2187) and the Global Research Development Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT; NRF-2015K1A4A3046807). The biospecimens and data used in this study were provided by Asan Bio-Resource Center, Korea Biobank Network (2012-9[52]). The authors express their sincere gratitude to Dr Sang-min Lee (Department of Radiology, Asan Medical Center) for his assistance with the radiological analysis.

Author contributions

Study design: YMO and JHK. Clinical data collection and primary analysis: IJ and DKO. Genetic data quality control and analysis: JHL. All authors made substantial contributions to interpretation of data; and took part in drafting the article or revising it critically for important intellectual content.

Disclosure

The authors report no conflicts of interest in this work.