Increased MMP12 mRNA expression in induced sputum was correlated with airway eosinophilic inflammation in asthma patients: Evidence from bioinformatic analysis and experiment verification

Background: Asthma is a common chronic airway inflammatory disease worldwide. Studies on gene expression profiles in induced sputum may provide noninvasive diagnostic biomarkers and therapeutic targets for asthma.

Objective: To investigate mRNA expression of MMP12 in induced sputum and its relationship with asthma airway eosinophilic inflammation.

Methods: GSE76262 dataset was analyzed using R software, weighted gene coexpression network analysis (WGCNA), and protein-protein interaction (PPI) network construction. The top ten hub genes were screened with Cytoscape software (version 3.8.4). We then verified the mRNA expression of MMP12 in two other datasets (GSE137268 and GSE74075) via ROC curve estimates and our induced sputum samples using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Finally, we explored the correlation between MMP12 with asthmatic eosinophilic-related indicators.

Results: We obtained the top ten hub genes, namely, CCL17, CCL2, CSF1, CCL22, CCR3, CD69, FCGR2B, CD1C, CD1E, and MMP12 via expression profile screening and validation on the GSE76262 dataset. MMP12 was selected as the candidate gene through further validation on GSE137268 and GSE74075 datasets. Finally, we demonstrated that the mRNA expression of MMP12 is significantly upregulated in induced sputum of asthmatic patients (p < 0.05) and significantly correlated with eosinophilic-related indicators (p < 0.05). These findings indicated that MMP12 can act as a diagnostic biomarker for asthma.

Conclusion: Our study successfully identified and demonstrated that MMP12 is a potential diagnostic biomarker for asthma due to its high expression and association with eosinophilic-related indicators. The results of this study can provide novel insights into asthmatic diagnosis and therapy in the future.