A mitochondria-related 9-gene induced sputum signature for severe asthma: an integrative transcriptomic analysis with
Ruonan Hui1,2, Lecheng Zhang1,2, Zhenliang Han2
1Qingdao Medical College of Qingdao University, Qingdao, Shandong, China.
Objective:
Severe asthma is biologically heterogeneous, and airway biomarkers for disease stratification remain limited. We aimed to identify a mitochondria-related induced sputum transcriptomic signature associated with severe asthma.
Methods:
Public induced sputum microarray datasets GSE76262 (discovery) and GSE147880 (external validation) were analyzed. Mitochondrial activity was quantified by single-sample gene set enrichment analysis using MitoCarta 3.0. Severe asthma was compared with a combined non-severe asthma/healthy-control reference group. Weighted gene co-expression network analysis and LASSO logistic regression were used to derive a gene signature, followed by external validation, multivariable logistic regression, immune infiltration analysis, and nomogram construction.
Results:
Severe asthma showed 2,000 differentially expressed genes, including 196 mitochondria-related genes. Mito Score was lower in severe asthma and discriminated severe disease (AUC, 0.791). A Mito Score-associated co-expression module yielded candidates enriched in oxidative phosphorylation, thermogenesis, cellular respiration, and reactive oxygen species-related pathways. LASSO identified a 9-gene signature (CLC, IL18R1, SLC7A11, MARCH1, RBMS2, MAN2B2, SMOX, TTC15, and CD4) with AUCs of 0.892 in discovery and 0.758 in external validation. Risk score remained independently associated with severe asthma after adjustment for age and sex.
Conclusions:
Induced sputum transcriptomics identified a reproducible mitochondria-related 9-gene signature associated with severe asthma, supporting mitochondrial dysfunction as a clinically relevant airway feature and a candidate biomarker framework for disease stratification.
