title: 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.
authors.affiliation: Department of Physiology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Geetanjali
authors.initials: G
authors.lastname: Bade
authors.affiliation: Program in Physiology and Experimental Medicine, The Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Meraj Alam
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Physiology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Akhilesh Kumar
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: Department of Physiology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Parul
authors.initials: P
authors.lastname: Khare
authors.affiliation: Department of Physiology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Krishna Kumar
authors.initials: KK
authors.lastname: Solaiappan
authors.affiliation: Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Randeep
authors.initials: R
authors.lastname: Guleria
authors.affiliation: Program in Physiology and Experimental Medicine, The Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Nades
authors.initials: N
authors.lastname: Palaniyar
authors.affiliation: Department of Physiology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Anjana
authors.initials: A
authors.lastname: Talwar
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D040081:Protein Array Analysis; D060066:Protein Interaction Maps; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology; D012307:Risk Factors; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects / Q000276:immunology; D013147:Spirometry; D014797:Vital Capacity
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators
keywords: Bio-Plex assay; COPD; biomarkers; networking; pathways