- Title
- Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes
- Creator
- Baines, Katherine J.; Simpson, Jodie L.; Wood, Lisa G.; Scott, Rodney J.; Fibbens, Naomi L.; Powell, Heather; Cowan, Douglas C.; Taylor, D. Robin; Cowan, Jan O.; Gibson, Peter G.
- Relation
- NHMRC
- Relation
- Journal of Allergy and Clinical Immunology Vol. 133, Issue 4, p. 997-1007
- Publisher Link
- http://dx.doi.org/10.1016/j.jaci.2013.12.1091
- Publisher
- Mosby
- Resource Type
- journal article
- Date
- 2014
- Description
- Background: Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms. Objective: This study aimed to identify and validate a sputum gene expression signature that discriminates asthma inflammatory phenotypes. Methods An asthma phenotype biomarker discovery study generated gene expression profiles from induced sputum of 47 asthmatic patients. A clinical validation study (n = 59 asthmatic patients) confirmed differential expression of key genes. A 6-gene signature was identified and evaluated for reproducibility (n = 30 asthmatic patients and n = 20 control subjects) and prediction of inhaled corticosteroid (ICS) response (n = 71 asthmatic patients). Receiver operating characteristic curves were calculated, and area under the curve (AUC) values were reported. Results: From 277 differentially expressed genes between asthma inflammatory phenotypes, we identified 23 genes that showed highly significant differential expression in both the discovery and validation populations. A signature of 6 genes, including Charcot-Leydon crystal protein (CLC); carboxypeptidase A3 (CPA3); deoxyribonuclease I-like 3 (DNASE1L3); IL-1ß (IL1B); alkaline phosphatase, tissue-nonspecific isozyme (ALPL); and chemokine (C-X-C motif) receptor 2 (CXCR2), was reproducible and could significantly (P <.0001) discriminate eosinophilic asthma from other phenotypes, including patients with noneosinophilic asthma (AUC, 89.6%), paucigranulocytic asthma (AUC, 92.6%), or neutrophilic asthma (AUC, 91.4%) and healthy control subjects (AUC, 97.6%), as well as discriminating patients with neutrophilic asthma from those with paucigranulocytic asthma (AUC, 85.7%) and healthy control subjects (AUC, 90.8). The 6-gene signature predicted ICS response (>12% change in FEV₁; AUC, 91.5%). ICS treatment reduced the expression of CLC, CPA3, and DNASE1L3 in patients with eosinophilic asthma. Conclusions: A sputum gene expression signature of 6 biomarkers reproducibly and significantly discriminates inflammatory phenotypes of asthma and predicts ICS treatment response. This signature has the potential to become a useful diagnostic tool to assist in the clinical diagnosis and management of asthma.
- Subject
- asthma; inflammatory phenotypes; gene expression; induced sputum; neutrophils; eosinophils
- Identifier
- http://hdl.handle.net/1959.13/1304225
- Identifier
- uon:20832
- Identifier
- ISSN:0091-6749
- Language
- eng
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