Single-cell and transcriptomic analyses identify PANoptosis–mitochondria-associated biomarkers with diagnostic and therapeutic potential in sepsis

Sepsis is a severe syndrome characterized by programmed cell death and organ dysfunction. The association between PANoptosis and mitochondrial dysfunction in sepsis remains unclear. This study aimed to investigate their relationship and identify potential biomarkers for diagnosis and treatment. Transcriptomic and single-cell RNA sequencing (scRNA-seq) data from the GEO database were analyzed to identify differentially expressed genes. Machine learning algorithms and scRNA-seq were used to identify biomarkers and investigate their expression levels at the single-cell level, followed by experimental validation using reverse transcription followed by polymerase chain reaction (qRT-PCR) and Western blot. Four biomarkers—BCL2, C1QBP, AIFM1, and BCL2L1—were identified and incorporated into a nomogram with high predictive accuracy (AUC: 0.983). scRNA-seq analysis revealed differential expression in macrophages, and experiments confirmed decreased AIFM1, BCL2, and C1QBP levels and increased BCL2L1 levels in septic mice. This study highlights the role of the PANoptosis–mitochondrial dysfunction in sepsis and identifies biomarkers with significant diagnostic and therapeutic potential.