Circulating syndecan-1 as a novel biomarker relates to lung function, systemic inflammation, and exacerbation in COPD

Abstract

Introduction

Patients with COPD often show increased systemic inflammation which is associated with lower functional status, greater exacerbation risk, and worse clinical outcomes. Syndecans (SDCs), a family of transmembrane heparan sulfate proteoglycans (HSPGs), have been found to involve in inflammatory processes in many chronic inflammatory diseases. The aim of this preliminary clinical study was to investigate the possible association between two SDCs, SDC-1 and SDC-4, with lung function, systemic inflammation, and risk of exacerbations in COPD patients.

Method

Serum SDC-1 and SDC-4 levels were measured in 101 COPD patients and 57 health controls. Correlations between SDCs and other parameters were analyzed using Spearsman’s rho. Receiver operating curve (ROC) analysis was used to evaluate the threshold value in differentiating disease status.

Results

Although both serum SDC-1 and SDC-4 showed a downward trend in COPD patients, only SDC-1 levels were correlated positively with the ratio of FEV1/FVC and parameters of small airway obstruction. Besides, SDC-1 but not SDC-4, was negatively correlated with C-reactive protein (CRP) in COPD patients and downregulated in frequent exacerbators (FEs) of COPD. Using a cutoff value of 2.08 ng/mL, the sensitivity and specificity of SDC-1 to differentiate FE were 44% and 93.4%, respectively.

Conclusion

In conclusion, circulating SDC-1 may be a novel inflammatory biomarker associated with lung function and systemic inflammation in patients with COPD, which could also be useful to identify the risk of COPD exacerbation. Further studies should be performed to clarify the influences of SDC-1 on the pathogenesis and outcomes of COPD.

Keywords:

• syndecan
• chronic obstructive pulmonary disease
• systemic inflammation
• exacerbation
• biomarker

Supplementary material

Figure S1 Serum SDC-1 correlated positively with the ratio of FEV1/FVC (A) and the parameters of small airway obstruction (SAO) (B-D) in all subjects.

Abbreviations: FEV1, forced expiratory volume in one second; FVC, forced vital capacity; SDC, syndecan.

Acknowledgments

This work was supported by National Key Research and Development Program (2016YFC0903600 and 2016YFC1304500), National Natural Science Foundation of China (81470236, 81670038 and 81830001), 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (2018HXFH017) and Health and Family Planning Commission of Sichuan Province (17PJ009). The funders had no role in study design, data collection or analysis, decision to publish, and manuscript preparation. We also thank Dr Haiqiao Wu for providing assistance in data collection.

Author contributions

Diandian Li, Yanqiu Wu, Shujin Guo, Lei Chen, and Fuqiang Wen designed this research, and all authors contributed toward subjects recruit, data collection, statistical analysis, drafting, and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.