Whole genome expression profiling in multiple trauma patients

Introduction

Severe trauma may be followed by an uncontrolled inflammatory response that is associated with high mortality and morbidity and the patient is at high risk of developing MOF [1]. Serial gene expression analysis of peripheral blood obtained from patients with polytrauma should provide a molecular portrait of mechanisms leading to sepsis. Genome-wide transcriptional profiling will permit identification of novel predictive biomarkers for earlier diagnosis of sepsis and MOF than current strategies using serum markers and clinical scores.

Methods

Whole blood Paxgene samples were collected at the initial time point (TP 0) and then every 24 hours until day 28 post hospital admission from 21 patients with multiple trauma. Ten patients developed sepsis during the stay in the ICU while 11 remained nonseptic. Total RNA was isolated from peripheral blood of each patient at TP 0 and subjected to microarray analysis using the CodeLink UniSet Human I Bioarray (Amersham Bioscience) containing 9877 human genes. Data analysis was carried out using ImaGene5 (Amersham Bioscience), dChip http://www.dchip.org and SAM http://www-stat.stanford.edu.

Results

Multiple testing with a FDR of 1.1 [2] revealed in total 692 significantly regulated genes in septic patients at TP 0, of which 480 genes had significantly higher and 212 genes significantly lower expression levels compared with nonseptic patients at TP 0. The highly expressed genes were mainly involved in inflammatory and stress responses, apoptosis and development, while the lower expressed genes could be assigned to defense responses, protein biosynthesis and lipid binding. Hierarchical clustering of the samples clearly differentiated between the time point of admission and sepsis.

Conclusion

Statistical analysis of expression data enabled clear differentiation between nonseptic and septic traumatic patients at admission to the ICU (TP 0). Septic patients showed significant overexpression of genes involved in immune responses and antiapoptosis, indicating a strong inflammatory interaction at time of admission as compared with nonseptic patients. The early vigorous inflammatory response appears to activate a program, subsequently leading to SIRS and, finally, MOF.