CSTA and DDX24: potential biomarkers regulating ferroptosis in sepsis and their diagnostic value

Sepsis is a critical condition involving dysregulated immune and metabolic responses. Ferroptosis has been implicated in its pathogenesis. However, the precise molecular mechanisms governing ferroptosis in sepsis remain unclear. Multiple transcriptomic datasets related to sepsis were comprehensively analyzed to screen potential hub genes. Differential expression profiling, weighted gene co-expression network construction, and three distinct machine learning approaches were applied in combination. To further elucidate the cellular distribution of these genes, single-cell RNA sequencing data were analyzed, and a corresponding miRNA–mRNA interaction network was established. The biological significance of the identified candidates was subsequently verified through in vitro functional experiments. Two core genes were identified. CSTA was significantly upregulated in sepsis and positively correlated with neutrophil infiltration and M1 macrophage polarization. DDX24 was markedly downregulated and positively associated with CD8⁺ T cell and NK cell function. Both genes demonstrated strong diagnostic performance (AUC > 0.87) in validation cohorts. In vitro modulation of these genes revealed that CSTA knockdown or DDX24 overexpression enhanced cell viability and reversed dysregulation of ferroptosis-related proteins, including upregulation of GPX4 and SLC7A11 and downregulation of ACSL4. CSTA and DDX24 are central regulators of ferroptosis in sepsis, exhibiting diagnostic and therapeutic potential.