Der Einfluss klinischer Entitäten auf die Überexpression genetischer Funktionsgruppen in Monozyten polytraumatisierter Patienten Eine Genom-weite Sicht

Abstract

Background: Posttraumatic immune system activation in patients after multiple, major trauma is closely linked to the development of SIRS (Systemic Inflammatory Response Syndrome, MODS (Multiple Organ Dysfunction Syndrome) and finally to the patients’ outcome. Recent publications and our own pre-work suggested that there are gene expression profiles, which can be significantly correlated to clinical parameters in the early posttraumatic period. Nevertheless, the functional meaning of this differential gene regulation still remains unclear. The aim of this study was to analyze, if there are specific clinical parameters that provoke a characteristic over-expression of functional gene pathways. Patients and Methods: Thirteen patients after major trauma (ISS 10 Red blood cell units/24 h), injury severity (ISS cutoff 40 points) and multiple organ failure (MOF cut-off 4 points). Subsequently, the data were analyzed by supervised analysis, hierarchical clustering and prediction model calculation. The biological relevance of the identified factors was evaluated using pathway analysis (www.ingenuity.com). Results: Gene expression profiles of patients after massive transfusion (224 probe sets) and such who deceased (763 probe sets) mainly consist of gene products, which play a role in »immunological activation«, »cellular movement« and »haematological system development and function«. Though the functional genetic groups seem to be similar in both analyses, only 6 genes are absolutely identical. Differentially expressed genes concerning multiple organ failure (660), are mainly associated to the functional groups »cancer« and »cell death«. Injury severity (295) chiefly leads to an over-expression of genes involved in common inflammatory reactions. Conclusion: We exhibited for the first time a serial, sequential screening analysis of monocyte mRNA expression patterns after multiple injury indicating a strongly significant connection between the patients’ gene profile and different clinical parameters. The latter provoke a characteristic over-expression of specific functional gene groups. Further studies to more in detail clarify clinical consequence of this different functional gene regulation are currently anticipated.