Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process.

Keywords:

• COPD
• Bio-Plex assay
• biomarkers
• pathways
• networking

Supplementary material

Figure S1 Flow diagram of the experimental design showing overall aim and analysis steps involved in the present study.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; VO₂, maximum oxygen uptake; BMI, body mass index; GOLD criteria, Global Initiative for Chronic Obstructive Lung Disease.

Table S1 Concentrations (pg/mL) of biomarkers detected in the sera samples among groups1*

Acknowledgments

The authors would like to thank all of the volunteers who took part in this study. The authors are also grateful to Dr Debabrata Ghosh, Department of Physiology, All India Institute of Medical Sciences, New Delhi, for his Molecular Biology laboratory facility support. This work was funded by the All India Institute of Medical Sciences, New Delhi, India (AT). MAK received postdoctoral fellowship support from the CIHR operating grant MOP-111012 to NP.

Disclosure

The authors report no conflicts of interest in this work.