Biomarker discovery and development in pediatric critical care medicine*

Abstract

Objective-To frame the general process of biomarker discovery and development, and to describe a proposal for the development of a multi-biomarker based risk model for pediatric septic shock.Data Source-Narrative literature review and author generated data.Main Results-Biomarkers can be grouped into four broad classes, based on the intended function: diagnostic, monitoring, surrogate, and stratification. Biomarker discovery and development requires a rigorous process, which is frequently not well followed in the critical care medicine literature. Very few biomarkers have successfully transitioned from the candidate stage to the true biomarker stage. There is great interest in developing diagnostic and stratification biomarkers for sepsis. Procalcitonin is currently the most promising diagnostic biomarker for sepsis. Recent evidence suggests that interleukin-8 can be used to stratify children with septic shock having a high likelihood of survival with standard care. Currently, there is a multiinstitutional effort to develop a multi-biomarker based sepsis risk model intended to predict outcome and illness severity for individual children with septic shock.Conclusions-Biomarker discovery and development is an important portion of the pediatric critical care medicine translational research agenda. This effort will require collaboration across multiple institutions and investigators. Rigorous conduct of biomarker-focused research holds the promise of transforming our ability to care for individual patients and our ability to conduct clinical trials in a more effective manner.

Clinical review: Sepsis and septic shock - the potential of gene arrays

“…The foundation of this effort is the relatively unbiased selection of a panel of candidate outcome biomarkers using microarray data from a large cohort of children with septic shock [56,57]. …”

Sepsis in Children

“…These inflammatory biomarkers are not recommended in routine testing [23,24]. CRP and procalcitonin have been helpful in certain cases.…”

Differential expression of the nuclear-encoded mitochondrial transcriptome in pediatric septic shock

“…The database has enabled the discovery of gene expression-based subclasses of pediatric septic shock [21][22][23], stratification biomarkers [24][25][26][27][28][29][30][31], diagnostic biomarkers [32][33][34][35], and novel therapeutic targets [36][37][38][39][40][41][42]. Here, we mined the database to test the hypothesis that expression of whole blood-derived nuclear-encoded mitochondrial genes will be differentially regulated between pediatric patients with septic shock and nonseptic controls within the first 24 hours of presentation to the PICU.…”