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. 2021 Feb 27;22(1):74.
doi: 10.1186/s12931-021-01665-4.

CiliOPD: a ciliopathy-associated COPD endotype

Jeanne-Marie Perotin  1   2 , Myriam Polette  1   3 , Gaëtan Deslée  1   2 , Valérian Dormoy  4
Affiliations

CiliOPD: a ciliopathy-associated COPD endotype

Jeanne-Marie Perotin et al. Respir Res. .

Abstract

The pathophysiology of chronic obstructive pulmonary disease (COPD) relies on airway remodelling and inflammation. Alterations of mucociliary clearance are a major hallmark of COPD caused by structural and functional cilia abnormalities. Using transcriptomic databases of whole lung tissues and isolated small airway epithelial cells (SAEC), we comparatively analysed cilia-associated and ciliopathy-associated gene signatures from a set of 495 genes in 7 datasets including 538 non-COPD and 508 COPD patients. This bio-informatics approach unveils yet undescribed cilia and ciliopathy genes associated with COPD including NEK6 and PROM2 that may contribute to the pathology, and suggests a COPD endotype exhibiting ciliopathy features (CiliOPD).

Keywords: COPD; Cilia; Transcriptomic.

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Conflict of interest statement

Dr. Deslée reports personal fees from Nuvaira, personal fees from BTG/PneumRx, personal fees from Chiesi, personal fees from Boehringer, personal fees from Astra Zeneca, outside the submitted work. Dr. Dormoy reports personal fees from Chiesi outside the submitted work.

Figures

Fig. 1
Fig. 1
Study design. a Flow chart defining the selection of cilia/ciliopathy-associated genes analysed in the 4 whole lung tissues and 3 SAEC datasets. b Table summarizing the available clinical parameters across the 7 datasets in non-COPD (N-COPD) and COPD patients
Fig. 2
Fig. 2
Identification of cilia-associated deregulated genes in COPD whole lung tissues. a dot plots showing cilia-associated genes signature quantification and significant fold change in COPD lung tissues compared with non-COPD lung tissues per dataset. b Venn diagram of overlapping genes between the 4 datasets of whole-lung tissues regarding the 350 cilia-associated genes. c Truncated violin-plots showing mean and IQR for the expression levels of FOXJ1 and NEK6 for the 4 whole lung tissue datasets. *, p < 0.05; ***, p < 0.001 non-COPD vs COPD
Fig. 3
Fig. 3
Identification of cilia-associated deregulated genes in COPD SAEC. a Dot plots showing cilia-associated genes signature quantification and significant fold change in COPD SAEC compared with non-COPD SAEC per dataset. b Venn diagram of overlapping genes between the 3 datasets of SAEC regarding the 399 cilia-associated genes. c Truncated violin-plots showing mean and IQR for the expression levels of FOXJ1 and PROM2 for the 3 SAEC datasets. *, p < 0.05; ***, p < 0.001 non-COPD vs COPD
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