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BMJ Open Respir Res . Ferroptosis-associated genes as candidate biomarkers for the identification of patients with severe influenza necessitating me

tetano

Editor, Senior Moderator
BMJ Open Respir Res


. 2025 Nov 10;12(1):e002557.
doi: 10.1136/bmjresp-2024-002557. Ferroptosis-associated genes as candidate biomarkers for the identification of patients with severe influenza necessitating mechanical ventilation

Xiaohui Mei[SUP] 1 [/SUP], Jie Hua[SUP] 2 [/SUP], Liang Chen[SUP] 3 [/SUP]



Affiliations
Free article Abstract

Background: Ferroptotic cell death is a highly regulated process characterised by the iron-dependent accumulation of lipid peroxides on cell membranes. However, the role of ferroptosis-related genes (FRGs) in severe influenza is not well characterised.
Methods: Influenza-related gene expression data and FRG lists were, respectively, downloaded from the gene expression omnibus and ferroptosis database. Differentially expressed FRGs (DE-FRGs) were then identified by comparing samples from patients with and without severe influenza, respectively, defined by patients who did and did not require mechanical ventilation. Enrichment analyses of these DE-FRGs were performed, and hub genes were subsequently identified, enabling the establishment of hub gene-drug interaction and competing endogenous RNA (ceRNA) networks.
Results: In total, these analyses revealed 171 DE-FRGs from patients with and without severe influenza. Least absolute shrinkage and selection operator and support vector machine-recursive feature elimination algorithms were used to identify eight hub genes from this dataset (ALOX12, MUC1, stearoyl-CoA desaturase, DECR1, EZH2, toll-like receptor 4 (TLR4), RICTOR and GSTM1), all of which exhibited good diagnostic utility for severe influenza. Functional enrichment analyses indicated that these genes may influence influenza pathogenesis through the regulation of immune and inflammatory responses. Single-sample gene set enrichment analysis approaches indicated that the expression levels for these hub DE-FRGs were negatively correlated with lymphocyte activity, whereas they were positively correlated with inflammatory cell activity. Predictive analyses additionally enabled the identification of 71 drugs targeting five of these genes, while ceRNA network diagrams highlighted the complex regulatory relationships among these genes.
Conclusion: The eight hub FRGs established in this study may play an important role in shaping the pathogenesis of severe influenza in individuals and may offer value as biomarkers that can guide the personalised prevention and treatment of this severe form of disease.

Keywords: Respiratory Infection; Viral infection.

 
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