Plasma sE-cadherin and the plasma sE-cadherin/sVE-cadherin ratio are potential biomarkers for chronic obstructive pulmonary disease

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs).

Objective: The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD.

Methods: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control).

Results: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p < 0.0001). sE-cadherin levels paralleled the severity of airflow limitation in both plasma (p < 0.01) and ELF (p < 0.05), while plasma sVE-cadherin levels were inversely correlated with the extent of emphysema (p < 0.05). MMP-7 levels were correlated with sE-cadherin levels in ELF.

Conclusions: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.

Keywords:

• COPD
• E-cadherin
• VE-cadherin
• MMP-7
• biomarker

Acknowledgements

The authors would like to thank Professor Kazuhiro Yamaguchi (Tokyo Women’s Medical University) and the late Professor Akitoshi Ishizaka (Keio University) for their insightful comments for this study. They also appreciate the technical assistance of Ms. Miyuki Yamamoto (Keio University).

Disclosure statement

TB has participated in an advisory board for GlaxoSmithKline. The other authors declare that there is no conflict of interest regarding the publication of this article.

Authorship

Shirahata S was involved in study design, analyzed the clinical data, and wrote the manuscript. Nakamura H designed the study and wrote the paper. Nakajima T, Nakamura M and Chubachi S took part in Chest CT-assessment and clinical analysis. Yoshida S and Tsuduki K coordinated the assay of the blood samples and data analysis. Minematsu N and Tateno H were involved in clinical assessment and data analysis. Mashimo S and Takahasi S took part in pulmonary function tests and clinical analysis. Asano K and Fujishima S were involved in study design and clinical assessment. Betsuyaku T supervised the study and wrote the paper.

Additional information

Funding

This study was supported in part by a grant to the Respiratory Failure Research Group from the Ministry of Health, Labour and Welfare of Japan.