Drp1-associated genes implicated in sepsis survival

Area of Science:

• Biochemistry
• Genetics
• Critical Care Medicine

Background:

• Sepsis is a life-threatening condition with high mortality, necessitating improved prognostic markers.
• Current treatments for sepsis are often inadequate, highlighting the need for better patient management tools.
• Mitochondrial dynamics, involving fission and fusion, are increasingly recognized as relevant to sepsis severity and inflammation.

Purpose of the Study:

• To engineer novel, reliable blood-borne biomarkers for predicting sepsis survival risk.
• To identify gene signatures associated with mitochondrial dynamics and sepsis prognosis.
• To validate these biomarkers in human transcriptomic datasets.

Main Methods:

• Utilized dynamin-related protein 1 (Drp1) and its associated genes.
• Developed a 12-gene signature (GS) based on differentially expressed genes (DEGs).
• Created a 7-gene protein-protein interaction (PPI)-based GS by comparing Drp1 interactors with sepsis survival genes.
• Validated both GSs using public human blood transcriptomic data from sepsis patients.

Main Results:

• Both DEG-based and PPI-based gene signatures demonstrated successful prediction of sepsis survival.
• The PPI-based 7-gene GS exhibited enhanced prognostic performance compared to the DEG-based GS.
• The developed biomarkers showed high sensitivity and specificity in both discovery and validation cohorts.

Conclusions:

• A novel, validated blood-borne biomarker (PPI-based 7-gene GS) for sepsis survival risk prediction has been engineered.
• This biomarker can aid in the early identification of high-risk sepsis patients.
• The findings support the potential for optimizing personalized treatment strategies to reduce sepsis mortality.