@article {KuoPA4890, author = {Chih Hsi Kuo and Yike Guo and Ioannis Pandis and Stelios Pavlidis and Uruji Hoda and Christos Rossios and Anthony Rowe and Susan J. Wilson and Peter Howarth and Ratko Djukanovic and Matthew J. Loza and Fred Baribaud and Peter J. Sterk and Ian M. Adcock and Kian Fan Chung}, title = {MMP10 and MET as predictive classifiers of bronchial eosinophilic asthma in UBIOPRED}, volume = {46}, number = {suppl 59}, elocation-id = {PA4890}, year = {2015}, doi = {10.1183/13993003.congress-2015.PA4890}, publisher = {European Respiratory Society}, abstract = {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.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/46/suppl_59/PA4890}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }