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Drp1-associated genes implicated in sepsis survival.

Marissa D Pokharel1,2, Anlin Feng1,3, Ying Liang1,3

  • 1Center for Translational Science, Florida International University, Port Saint Lucie, FL, United States.

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|January 23, 2025
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New blood biomarkers predicting sepsis survival risk have been developed. These markers, based on mitochondrial dynamics genes, can improve early patient identification and treatment strategies, potentially reducing sepsis mortality.

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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.