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Gene expression profiles are influenced by ISS, MOF, and clinical outcome in multiple injured patients: a genome-wide comparative analysis

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Abstract

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.

Patients and 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.

Conclusion

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.

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Acknowledgements

The authors wish to gratefully acknowledge the technical support of the National Institutes of General Medical Sciences’ funded Large Scale Collaborative Research Program (U54-GM-62119-02), entitled Inflammation and Host Response to Injury, awarded to Dr. Ronald G. Tompkins and Massachusetts General Hospital which provided technical assistance with the sample preparation, cRNA synthesis, and microarray analysis. The authors have no conflicting financial interests. Analyses were performed using BRB Array Tools developed by Dr. Richard Simon and Amy Peng and DChip (Wong Laboratory, Department of Biostatistics, Harvard School of Public Health, USA).

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Authors and Affiliations

  1. Chirurgische Klinik und Poliklinik-Innenstadt, Ludwig-Maximilians University, Nussbaumstrasse 20, 80336, Munich, Germany

    V. Bogner, C. Kirchhoff, J. C. Stegmaier, W. Mutschler & P. Biberthaler

  2. Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, 32610-0266, USA

    H. V. Baker

  3. Department of Surgery, Laboratory of Inflammation Biology and Surgical Science, University of Florida College of Medicine, Shands Hospital, 1600 SW Archer Road, Gainesville, FL, 32610-0286, USA

    L. L. Moldawer

Authors
  1. V. Bogner
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  2. C. Kirchhoff
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  3. H. V. Baker
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  4. J. C. Stegmaier
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  5. L. L. Moldawer
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  6. W. Mutschler
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  7. P. Biberthaler
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Corresponding author

Correspondence to V. Bogner.

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Best abstracts — Surgical Forum 2007

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Bogner, V., Kirchhoff, C., Baker, H.V. et al. Gene expression profiles are influenced by ISS, MOF, and clinical outcome in multiple injured patients: a genome-wide comparative analysis. Langenbecks Arch Surg 392, 255–265 (2007). https://doi.org/10.1007/s00423-007-0182-5

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  • DOI: https://doi.org/10.1007/s00423-007-0182-5

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