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.
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