Identification and validation of core oxidative phosphorylation-related genes as biomarkers for immune response and diagnosis in burn injury.

INTRODUCTION: Burn injuries are a common and devastating trauma that induce profound alterations in the immune microenvironment and further influence patient recovery and clinical outcomes. This study aimed to characterize the immune landscape of burn patients and identify key biomarkers for early diagnosis and targeted therapeutic strategies. METHODS: Transcriptomic data from the GSE37069 and GSE19743 datasets were used for differential expression analysis to screen oxidative phosphorylation-related genes. Three machine learning algorithms (SVM-RFE, Random Forest, and Lasso) were combined to shortlist core genes. The differential expression of candidate genes was validated by qPCR and Western blot in burn tissues. Immune cell infiltration profiles were analyzed with the CIBERSORT algorithm. Correlation analysis was performed between core genes and immune cell subsets. Gene silencing assays in LPS-stimulated THP-1-derived macrophages were conducted to explore functional mechanisms, and a diagnostic nomogram was constructed to evaluate diagnostic performance. RESULTS: A total of 23 oxidative phosphorylation-related differentially expressed genes were identified. Three core genes - ATP6V1C1, ECHS1, and LDHA - were screened out and confirmed to be significantly associated with burn progression. Immune infiltration analysis revealed distinct immune cell compositions between two patient groups: patients in group A exhibited a more active immune response with increased levels of B cells, M0 macrophages, and CD4+ memory T cells, while group B patients had higher proportions of CD8+ T cells and resting NK cells, indicating a more tolerogenic immune state. Correlation analysis suggested that ECHS1 may be involved in modulating immune cell activity, whereas ATP6V1C1 and LDHA may participate in the early immune response. In vitro validation showed that knockdown of ATP6V1C1 or LDHA markedly attenuated the secretion of pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ), as well as mitochondrial reactive oxygen species production and oxygen consumption; by contrast, ECHS1 knockdown further amplified the inflammatory response. The diagnostic nomogram based on the three core genes demonstrated excellent diagnostic performance. DISCUSSION: These findings provide valuable insights into the immunological dynamics of burn patients. The identified core genes highlight potential molecular targets for improving prognosis and therapeutic outcomes, and the nomogram offers a promising tool for burn patient stratification and personalized treatment.