Validation of S100A16 as an asthma biomarker and its role in IL-13-induced bronchial epithelial cell injury.

BACKGROUND: Asthma is a heterogeneous chronic inflammatory disease of the airway, and its development is the result of genetic factors, environmental factors, immune dysfunction, and other factors. This study aimed to identify biomarkers of asthma. METHODS: A differential gene expression (DGE) analysis and a weighted gene co-expression network analysis (WGCNA) were conducted to identify the asthma-related genes in the GSE67472 dataset, and these genes were intersected with immune genes from the Immuport database to identify the asthma-associated immune genes. Least absolute shrinkage and selection operator (LASSO) regression was used to identify the key asthma-associated immune genes, and receiver operating characteristic (ROC) curves were used to assess the diagnostic potential of these genes. Subsequently, the mechanism of action of the inducible factor interleukin 13 (IL-13) in human bronchial epithelial (HBE) cells and its effect on markers of asthma were verified in vitro. RESULTS: The DGE analysis and WGCNA identified 62 asthma-related genes, and eight asthma-associated immune genes were identified after the intersection of the asthma-related genes and the immune-related genes. Utilizing LASSO regression, five key immune genes linked to asthma were uncovered. These included S100 calcium binding protein A16 (S100A16), Lactotransferrin (LTF), BPI fold containing family A member 1 (BPIFA1), cystatin 4 (CST4), and growth-related protein (GRP). The area under the curve (AUC) values of S100A16 and CST4 were greater than 0.8. The single-cell analysis showed that S100A16 was highly expressed in asthmatic neutrophils. Finally, the results of the in vitro experiments showed that IL-13 not only induced lipid peroxidation to promote iron death in the HBE cells, but also promoted the expression of S100A16. CONCLUSIONS: This study identified a new biomarker, S100A16, for the diagnosis of asthma. S100A16 may serve as a new potential target for asthma treatment, and may be an important regulator of ferroptosis.