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Validation of a gene expression-based subclassification strategy for pediatric septic shock
Hector R Wong1, Natalie Z Cvijanovich, Geoffrey L Allen
1Department of Pediatrics, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA. hector.wong@cchmc.org
Critical Care Medicine
|June 28, 2011
Summary
Researchers validated three septic shock subclasses in children using a 100-gene expression signature. These subclasses show distinct clinical differences, aiding patient management and clinical trials.
Area of Science:
- Pediatric critical care medicine
- Molecular biology
- Bioinformatics
Background:
- Septic shock exhibits significant heterogeneity, complicating clinical trials and patient care.
- Previous research identified three potential septic shock subclasses in children based on a 100-gene expression signature.
Purpose of the Study:
- To prospectively validate the previously identified gene expression-based subclasses of pediatric septic shock.
- To confirm the clinical relevance and distinct characteristics of these subclasses in a new cohort.
Main Methods:
- Prospective observational study utilizing microarray-based bioinformatics.
- Analysis of separate derivation (n=98) and validation (n=82) cohorts of children with septic shock.
- Classification of patients into subclasses A, B, or C using computer-based image analysis of gene expression mosaics.
Main Results:
- The 100-gene signature successfully classified 82 children in the validation cohort into three subclasses.
- Subclass A exhibited higher illness severity, greater organ failure, fewer intensive care unit-free days, and higher Pediatric Risk of Mortality scores.
- Subclass A patients showed repressed adaptive immunity and glucocorticoid receptor signaling genes. Clinician consensus showed modest agreement with the algorithm.
Conclusions:
- The existence of distinct subclasses in pediatric septic shock, defined by a 100-gene expression signature, has been prospectively validated.
- These gene expression-based subclasses possess clinically significant differences, offering potential for improved patient stratification and management.
