Gene expression profiles are influenced by ISS, MOF, and clinical outcome in multiple injured patients: a genome-wide comparative analysis.
BACKGROUND
Posttraumatic immune system activation in major trauma patients is linked to systemic inflammatory response syndrome, multiple organ failure (MOF), and mortality. Recent studies suggest that genome-wide expression is altered in response to distinct clinical parameters; however, the functional allocation of theses genes remains unclear.


METHODS
Thirteen patients after major trauma (Injury Severity Score < 16) were studied. Monocytes were obtained on admission (within 90 min) and at 6, 12, 24, 48, and 72 h after trauma. Complementary ribonucleic acid (RNA) targets were hybridized to Affymetrix HG U 133A microarrays. Searching for genes that are differentially expressed, the patients were dichotomously assigned depending upon survival, injury severity, and MOF. The data were analyzed by supervised analysis, clustering, and comparative pathway analysis.


RESULTS
Gene expression profiles of patients with adverse outcomes (763 probe sets) mainly consist of those involved in "immunological activation" or "cellular movement," whereas the gene set associated with MOF (660) is associated with "cancer" and "cell death." Injury severity (295) leads to an overexpression of genes involved in inflammatory disease.


CONCLUSIONS
We demonstrate for the first time a serial, sequential screening analysis of monocyte messenger RNA expression patterns after multiple injury indicating a strongly significant connection between the patients' expression profile and different clinical parameters. The latter provoke a characteristic overexpression of specific functional gene ontologies. Further studies to clarify clinical consequence of this differential gene regulation are currently anticipated.
Bogner
V
V
Chirurgische Klinik und Poliklinik-Innenstadt, Ludwig-Maximilians University, Nussbaumstrasse 20, 80336 Munich, Germany. Viktoria.Bogner@med.uni-muenchen.de
Kirchhoff
C
C
Baker
H V
HV
Stegmaier
J C
JC
Moldawer
L L
LL
Mutschler
W
W
Biberthaler
P
P
D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D009102:Multiple Organ Failure / Q000235:genetics*; D009104:Multiple Trauma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D015599:Trauma Severity Indices
D012333:RNA, Messenger