Abstract
PURPOSE: Sepsis, a life-threatening inflammatory condition due to an imbalanced response to infections, has been a major concern. Necroptosis, a newly discovered programmed cell death form, plays a crucial role in various inflammatory diseases. Our study aims to identify necroptosis - related genes (NRGs) and explore their potential for sepsis diagnosis. PATIENTS AND METHODS: We used weighted gene co-expression network analysis to identify gene modules associated with sepsis. Cox regression and Kaplan-Meier methods were employed to assess the diagnostic and prognostic value of these genes. Single-cell and immune infiltration analyses were carried out to explore the immune environment in sepsis. Plasma CD74 protein levels were quantified in our samples, and relevant clinical data from electronic patient records were analyzed for correlation. RESULTS: CD74 was identified through the intersection of the hub genes of sepsis and NRGs related modules. Septic patients had lower CD74 expression compared to healthy controls. The CD74-based diagnostic model showed better performance in the training dataset (AUC, 0.79 [95% CI, 0.75-0.84]), was cross-validated in external datasets, and demonstrated better performances than other published diagnostic models. Pathway analysis and single-cell profiling supported further exploration of CD74-related inflammation and immune response in sepsis. CONCLUSION: This study presents the first quantitative assessment of human plasma CD74 in sepsis patients. CD74 levels were significantly lower in the sepsis cohort. CD74 warrants further exploration as a potential prognostic and therapeutic target for sepsis.