Identification of differentially expressed oxidative stress-related genes in major burned patients and potential mechanisms based on hub genes

Background : Burns are extremely destructive injuries to the human body. Once a major burn occurs, it can lead to long-term disabilities, psychological burdens, and significant loss of human resources and economic losses. Extensive burns can cause severe oxidative stress, systemic inflammatory response, and a hypermetabolic state. Besides traditional symptomatic treatment, there is an urgent need for new approaches to address oxidative stress and internal environment disturbance in burn injuries. Methods : Based on the GEO database and the Limma R package, differential gene expression analysis was performed to identify genes differentially expressed in severe burns and genes associated with oxidative stress. The Gene Ontology (GO) database was used to analyze the cellular functions of these oxidative stress-related genes, and weighted gene co-expression networks analysis (WGCNA) and protein-protein interaction (PPI) networks were constructed. Receiver operating characteristic (ROC) curves were then constructed to identify hub genes in the networks. A diagnostic model based on these central genes was established using the least absolute shrinkage and selection operator (LASSO) analysis and ROC analysis. Immune-related functions were assessed by evaluating the correlation between the expression of hub genes and immune cell infiltration scores. Additionally, drug-gene interaction databases were used to predict target drugs, and miRNet was used to predict the regulation of miRNA and transcription factors. Results : Through differential analysis, a total of 2,899 differentially expressed genes, 4,936 WGCNA module genes, and 437 oxidative stress-related genes were identified, resulting in 44 candidate genes. Ten hub genes (GCLM, MMP9, BCL2, IL10, SIRT1, NME8, PINK1, GCLC, EPAS1, PARK7) were identified. These central genes were found to be enriched in GO annotations related to “starch and sugar metabolism,” “lysosomes,” and “actin cytoskeleton regulation.” Additionally, it is predicted that 78 drugs can target GCLM, MMP9, BCL2, IL10, SIRT1, NME8, PINK1, GCLC, EPAS1, PARK7, including cisplatin, curcumin, and bevacizumab. A hub gene-miRNA regulatory network with 168 miRNAs and a hub gene-transcription factor (TF) network with 15 TFs were also constructed. These hub genes may serve as biomarkers for the assessment and treatment of oxidative stress in major burns, and provide clues for potential new therapeutic targets. Conclusion : Based on the common genes associated with major burns and oxidative stress in this study, 10 target genes were proposed. These candidate genes may provide new insights into potential mechanisms for exploring the increased risk of burn severity changes caused by oxidative stress at the transcriptional level.