PT  - JOURNAL ARTICLE
AU  - Chih Hsi Kuo
AU  - Yike Guo
AU  - Ioannis Pandis
AU  - Stelios Pavlidis
AU  - Uruji Hoda
AU  - Christos Rossios
AU  - Anthony Rowe
AU  - Susan J. Wilson
AU  - Peter Howarth
AU  - Ratko Djukanovic
AU  - Matthew J. Loza
AU  - Fred Baribaud
AU  - Peter J. Sterk
AU  - Ian M. Adcock
AU  - Kian Fan Chung
TI  - <em>MMP10</em> and <em>MET</em> as predictive classifiers of bronchial eosinophilic asthma in UBIOPRED
AID  - 10.1183/13993003.congress-2015.PA4890
DP  - 2015 Sep 01
TA  - European Respiratory Journal
PG  - PA4890
VI  - 46
IP  - suppl 59
4099  - http://erj.ersjournals.com/content/46/suppl_59/PA4890.short
4100  - http://erj.ersjournals.com/content/46/suppl_59/PA4890.full
SO  - Eur Respir J2015 Sep 01; 46
AB  - Rationale: Airway inflammation of asthma involves diverse cell types. We hypothesize that gene expression profile of bronchial biopsy in asthma is associated with specific inflammatory cell infiltration.Methods: Bronchial biopsies were obtained from moderate/severe asthma cohort and gene expression analyzed. Submucosal inflammatory cell counts of eosinophil (EOS), neutrophil (NEU) and CD4+ T cell (CD4) were studied by immunohistochemistry. Each cell type was clustered by partition around medoids and support vector machine (Y Lee et al. Bioinformatics 2003 19:1132-39) was used to address classification.Results: 81 biopsy samples were available for analysis. 4 cluster medoids of IHC counts were noted for EOS (0, 2.2, 5.7 and 13.6/mm2), NEU (4.6, 12.1, 20.0 and 50.8/mm2) and CD4 (4.4, 12.2, 35.2 and 111.9/mm2). IHC counts of each higher two medoids (high group) were significantly higher than control. MMP10 (log2FC:1.31, adjusted-p=0.035) and MET (Met proto-oncogene) (log2FC:0.42, adjusted-p=0.035) were differentially expressed in the EOS high group (cutoff 4.0/mm2). The most differentially expressed genes in the CD4 high (DOCK10, adjusted-p=0.175) group did not reach statistical significance. ROC curve showed MMP10 and MET as classifiers of high bronchial EOS (AUC: 0.853, 95%CI: 0.758-0.937, p=3.97e-08), providing the overall best accuracy at 82.7%. Conclusion: MMP10 and MET are novel gene markers of bronchial eosinophilic asthma.