Identification and Functional Analysis of PANoptosis-Associated Genes in the Progression From Sepsis to ARDS.

Summary

Using transcriptomic analyses, immune correlation, Mendelian randomization, immunohistochemistry, and a murine sepsis model, the study identifies NDRG1 as upregulated in ARDS and causally linked to ARDS risk. Suppressing NDRG1 ameliorated sepsis-induced lung injury, positioning NDRG1 as a potential therapeutic target and biomarker for septic ARDS.

Key Findings

• A PRG-based diagnostic model discriminated septic ARDS from sepsis alone.
• NDRG1 was upregulated in ARDS; DDX3X, PTPRC, and TNFSF8 were downregulated.
• Mendelian randomization suggested a causal link between NDRG1 and ARDS.
• In a mouse sepsis model, NDRG1 suppression alleviated lung injury; IHC localized NDRG1 near vascular walls.

Clinical Implications

NDRG1 may serve as a biomarker and therapeutic target for septic ARDS; translation would require target validation, safety profiling, and early-phase trials.

Limitations

• Human transcriptomic cohorts and sample sizes are not detailed; external validation is lacking.
• Causal inference via MR depends on instrument validity; translational gaps from mouse to human remain.

Future Directions

Validate NDRG1 in independent human cohorts, dissect cell-type-specific PANoptosis mechanisms, and evaluate pharmacologic modulation of NDRG1 in preclinical models.