Identification of the potential role of PANoptosis-related genes in burns via bioinformatic analyses and experimental validation.

Background: The treatment of burns is highly challenging due to their complex pathophysiological mechanisms. PANoptosis, as an important form of cell death, is suggested to play a crucial role in the inflammatory response and tissue damage following burns. However, the role of PANoptosis-related biomarkers in the pathophysiological processes of burns remains unclear. In this study, we aim to identify PANoptosis-related signature genes and validate them as biomarkers in burns METHODS: Burn-related datasets were obtained from the Gene Expression Omnibus（GEO） database. GSE37069 was used for bioinformatic analysis and machine learning, while GSE19743 was used specifically for external validation. A set of PANoptosis-associated genes was obtained from the GeneCards database. Three machine learning models (LASSO, RF, and SVM-RFE) and WGCNA were utilized to screen for signature genes. The diagnostic efficacy of the identified genes was assessed through receiver operating characteristic (ROC) curves. Gene Set Enrichment Analysis (GSEA) was performed to identify pathways associated with the signature genes, while single-sample gene set enrichment analysis (ssGSEA) was employed to investigate the immune landscape. Finally, Western blotting and RT-qPCR were employed to validate the signature genes.

Results: BCL-2, CCAR1, CERK, TRIAP1, S100A8, and SNHG1 were identified as signature genes. The biological processes involving these genes mainly include endocytosis, apoptosis, and ECM receptor interaction. Immune infiltration analysis revealed that neutrophils, eosinophils, M0 macrophages, and monocytes are significantly elevated in burn samples. Additionally, these signature genes showed significant correlations with multiple immune cell types. Finally, Western blotting and RT-qPCR analysis revealed that the expression levels of BCL2, CCAR1, CERK, and TRIAP1 were significantly down-regulated in the burn groups compared to the normal groups, with the exception of S100A8.

Conclusion: Our study has identified BCL-2, CCAR1, CERK, and TRIAP1 as reliable potential biomarkers for burn injuries. These genes play crucial roles in immune response, wound healing, and anti-apoptotic mechanisms, which are key pathological processes involved in the progression of burn injuries. Specifically, BCL-2, CCAR1, CERK, and TRIAP1 have been shown to significantly impact the regulation of inflammation, the efficiency of wound repair, and the prevention of cell apoptosis during burn injury.