Insight into the role of mitochondrion-related gene anchor signature in mitochondrial dysfunction of neutrophilic asthma

Abstract

Objective At present, targeting molecular-pharmacological therapy is still difficult in neutrophilic asthma. The investigation aims to identify and validate mitochondrion-related gene signatures for diagnosis and specific targeting therapeutics in neutrophilic asthma. Methods Bronchial biopsy samples of neutrophilic asthma and healthy people were identified from the GSE143303 dataset and then matched with human mitochondrial gene data to obtain mitochondria-related differential genes (MitoDEGs). Signature mitochondria-related diagnostic markers were jointly screened by support vector machine (SVM) analysis, least absolute shrinkage, and selection operator (LASSO) regression. The expression of marker MitoDEGs was evaluated by validation datasets GSE147878 and GSE43696. The diagnostic value was evaluated by receiver operating characteristic (ROC) curve analysis. Meanwhile, the infiltrating immune cells were analyzed by the CIBERSORT. Finally, oxidative stress level and mitochondrial functional morphology for asthmatic mice and BEAS-2B cells were evaluated. The expression of signature MitoDEGs was verified by qPCR. Results 67 MitoDEGs were identified. Five signature MitoDEGs (SOD2, MTHFD2, PPTC7, NME6, and SLC25A18) were further screened out. The area under the curve (AUC) of signature MitoDEGs presented a good diagnostic performance (more than 0.9). There were significant differences in the expression of signature MitoDEGs between neutrophilic asthma and non-neutrophilic asthma. In addition, the basic features of mitochondrial dysfunction were demonstrated by in vitro and in vivo experiments. The expression of signature MitoDEGs in the neutrophilic asthma mice presented a significant difference from the control group. Conclusions These MitoDEGs signatures in neutrophilic asthma may hold potential as anchor diagnostic and therapeutic targets in neutrophilic asthma.