Identification of sepsis subtypes in critically ill adults using gene expression profiling

Critical Care

Anthony S McLean¹  Benjamin M Tang³  David M Maslove² 

[1] Department of Intensive Care Medicine, Nepean Hospital and Nepean Clinical School, University of Sydney, Penrith, NSW 2750, Australia;Biomedical Informatics Training Program, Stanford University School of Medicine, Stanford, CA, USA;School of Public Health, Faculty of Medicine, University of Sydney, NSW 2006, Australia

关键词: intensive care;    critical care;    biomedical informatics;    microarray analysis;    gene expression profiling;    septic shock;    severe sepsis;    Sepsis;   

Others  :  820749
DOI  :  10.1186/cc11667

 received in 2012-02-28, accepted in 2012-10-04,  发布年份 2012

【 摘 要 】

Introduction

Sepsis is a syndromic illness that has traditionally been defined by a set of broad, highly sensitive clinical parameters. As a result, numerous distinct pathophysiologic states may meet diagnostic criteria for sepsis, leading to syndrome heterogeneity. The existence of biologically distinct sepsis subtypes may in part explain the lack of actionable evidence from clinical trials of sepsis therapies. We used microarray-based gene expression data from adult patients with sepsis in order to identify molecularly distinct sepsis subtypes.

Methods

We used partitioning around medoids (PAM) and hierarchical clustering of gene expression profiles from neutrophils taken from a cohort of septic patients in order to identify distinct subtypes. Using the medoids learned from this cohort, we then clustered a second independent cohort of septic patients, and used the resulting class labels to evaluate differences in clinical parameters, as well as the expression of relevant pharmacogenes.

Results

We identified two sepsis subtypes based on gene expression patterns. Subtype 1 was characterized by increased expression of genes involved in inflammatory and Toll receptor mediated signaling pathways, as well as a higher prevalence of severe sepsis. There were differences between subtypes in the expression of pharmacogenes related to hydrocortisone, vasopressin, norepinephrine, and drotrecogin alpha.

Conclusions

Sepsis subtypes can be identified based on different gene expression patterns. These patterns may generate hypotheses about the underlying pathophysiology of sepsis and suggest new ways of classifying septic patients both in clinical practice, and in the design of clinical trials.

【 授权许可】

   
2012 Maslove et al.; licensee BioMed Central Ltd.

【 图 表 】

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