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Published in: Langenbeck's Archives of Surgery 3/2007

01-05-2007 | Original Article

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

Authors: V. Bogner, C. Kirchhoff, H. V. Baker, J. C. Stegmaier, L. L. Moldawer, W. Mutschler, P. Biberthaler

Published in: Langenbeck's Archives of Surgery | Issue 3/2007

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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.
Literature
1.
go back to reference Baue AE, Durham R, Faist E (1998) Systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF): are we winning the battle? Shock 10(2):79–89PubMedCrossRef Baue AE, Durham R, Faist E (1998) Systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF): are we winning the battle? Shock 10(2):79–89PubMedCrossRef
2.
go back to reference Mannick JA, Rodrick ML, Lederer JA (2001) The immunologic response to injury. J Am Coll Surg 193(3):237–244PubMedCrossRef Mannick JA, Rodrick ML, Lederer JA (2001) The immunologic response to injury. J Am Coll Surg 193(3):237–244PubMedCrossRef
3.
go back to reference Baue AE (2000) Multiple organ failure−the discrepancy between our scientific knowledge and understanding and the management of our patients. Langenbeck’s Arch Surg 385(7):441–453CrossRef Baue AE (2000) Multiple organ failure−the discrepancy between our scientific knowledge and understanding and the management of our patients. Langenbeck’s Arch Surg 385(7):441–453CrossRef
4.
go back to reference Lederer JA, Rodrick ML, Mannick JA (1999) The effects of injury on the adaptive immune response. Shock 11(3):153–159PubMedCrossRef Lederer JA, Rodrick ML, Mannick JA (1999) The effects of injury on the adaptive immune response. Shock 11(3):153–159PubMedCrossRef
5.
go back to reference Biberthaler P, Bogner V, Baker HV, Lopez MC, Neth P, Kanz KG et al (2005) Genome-wide monocytic mRNA expression in polytrauma patients for identification of clinical outcome. Shock 24(1):11–19PubMedCrossRef Biberthaler P, Bogner V, Baker HV, Lopez MC, Neth P, Kanz KG et al (2005) Genome-wide monocytic mRNA expression in polytrauma patients for identification of clinical outcome. Shock 24(1):11–19PubMedCrossRef
6.
go back to reference Committe on Injury Scaling (1990) Abbreviated injury scale 1990 revision. Association of the Advancement of Automovement Medicine, Des Plaines, Illinois, 2002 Committe on Injury Scaling (1990) Abbreviated injury scale 1990 revision. Association of the Advancement of Automovement Medicine, Des Plaines, Illinois, 2002
7.
go back to reference Li C, Wong WH (2001) Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci U S A 98(1):31–36PubMedCrossRef Li C, Wong WH (2001) Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci U S A 98(1):31–36PubMedCrossRef
8.
go back to reference Simon R, Radmacher MD, Dobbin K, McShane LM (2003) Pitfalls in the use of DNA microarray data for diagnostic and prognostic classification. J Natl Cancer Inst 95(1):14–18PubMedCrossRef Simon R, Radmacher MD, Dobbin K, McShane LM (2003) Pitfalls in the use of DNA microarray data for diagnostic and prognostic classification. J Natl Cancer Inst 95(1):14–18PubMedCrossRef
9.
go back to reference Botha AJ, Moore FA, Moore EE, Sauaia A, Banerjee A, Peterson VM (1995) Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure. J Trauma 39(3):411–417PubMedCrossRef Botha AJ, Moore FA, Moore EE, Sauaia A, Banerjee A, Peterson VM (1995) Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure. J Trauma 39(3):411–417PubMedCrossRef
10.
go back to reference Lefering R, Goris RJ, van Nieuwenhoven EJ, Neugebauer E (2002) Revision of the multiple organ failure score. Langenbeck’s Arch Surg 387(1):14–20CrossRef Lefering R, Goris RJ, van Nieuwenhoven EJ, Neugebauer E (2002) Revision of the multiple organ failure score. Langenbeck’s Arch Surg 387(1):14–20CrossRef
11.
go back to reference Grotz M, von Griensven M, Stalp M, Kaufmann U, Hildebrand F, Pape HC (2001) Scoring multiple organ failure after severe trauma. Comparison of the Goris, Marshall and Moore scores. Chirurg 72(6):723–730PubMedCrossRef Grotz M, von Griensven M, Stalp M, Kaufmann U, Hildebrand F, Pape HC (2001) Scoring multiple organ failure after severe trauma. Comparison of the Goris, Marshall and Moore scores. Chirurg 72(6):723–730PubMedCrossRef
12.
go back to reference Lee Y, Lee CK (2003) Classification of multiple cancer types by multicategory support vector machines using gene expression data. Bioinformatics 19(9):1132–1139PubMedCrossRef Lee Y, Lee CK (2003) Classification of multiple cancer types by multicategory support vector machines using gene expression data. Bioinformatics 19(9):1132–1139PubMedCrossRef
13.
go back to reference Shinozaki M, Hirahashi J, Lebedeva T, Liew FY, Salant DJ, Maron R et al (2002) IL-15, a survival factor for kidney epithelial cells, counteracts apoptosis and inflammation during nephritis. J Clin Invest 109(7):951–960PubMedCrossRef Shinozaki M, Hirahashi J, Lebedeva T, Liew FY, Salant DJ, Maron R et al (2002) IL-15, a survival factor for kidney epithelial cells, counteracts apoptosis and inflammation during nephritis. J Clin Invest 109(7):951–960PubMedCrossRef
14.
go back to reference Budagian V, Bulanova E, Paus R, Bulfone-Paus S (2006) IL-15/IL-15 receptor biology: a guided tour through an expanding universe. Cytokine Growth Factor Rev 17(4):259–280PubMedCrossRef Budagian V, Bulanova E, Paus R, Bulfone-Paus S (2006) IL-15/IL-15 receptor biology: a guided tour through an expanding universe. Cytokine Growth Factor Rev 17(4):259–280PubMedCrossRef
15.
go back to reference Zingarelli B, Cook JA (2005) Peroxisome proliferator-activated receptor-gamma is a new therapeutic target in sepsis and inflammation. Shock 23(5):393–399PubMedCrossRef Zingarelli B, Cook JA (2005) Peroxisome proliferator-activated receptor-gamma is a new therapeutic target in sepsis and inflammation. Shock 23(5):393–399PubMedCrossRef
16.
go back to reference Gierens H, Nauck M, Roth M, Schinker R, Schurmann C, Scharnagl H et al (2000) Interleukin-6 stimulates LDL receptor gene expression via activation of sterol-responsive and Sp1 binding elements. Arterioscler Thromb Vasc Biol 20(7):1777–1783PubMed Gierens H, Nauck M, Roth M, Schinker R, Schurmann C, Scharnagl H et al (2000) Interleukin-6 stimulates LDL receptor gene expression via activation of sterol-responsive and Sp1 binding elements. Arterioscler Thromb Vasc Biol 20(7):1777–1783PubMed
17.
go back to reference Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374(Pt 1):1–20PubMedCrossRef Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374(Pt 1):1–20PubMedCrossRef
18.
go back to reference Giannoudis PV, Hildebrand F, Pape HC (2004) Inflammatory serum markers in patients with multiple trauma. Can they predict outcome? J Bone Joint Surg Br 86(3):313–323PubMedCrossRef Giannoudis PV, Hildebrand F, Pape HC (2004) Inflammatory serum markers in patients with multiple trauma. Can they predict outcome? J Bone Joint Surg Br 86(3):313–323PubMedCrossRef
19.
go back to reference Weiss DJ, Welle M, Mortiz A, Walcheck B (2004) Evaluation of leukocyte cell surface markers in dogs with septic and nonseptic inflammatory diseases. Am J Vet Res 65(1):59–63PubMedCrossRef Weiss DJ, Welle M, Mortiz A, Walcheck B (2004) Evaluation of leukocyte cell surface markers in dogs with septic and nonseptic inflammatory diseases. Am J Vet Res 65(1):59–63PubMedCrossRef
20.
go back to reference Harter L, Mica L, Stocker R, Trentz O, Keel M (2003) Mcl-1 correlates with reduced apoptosis in neutrophils from patients with sepsis. J Am Coll Surg 197(6):964–973PubMedCrossRef Harter L, Mica L, Stocker R, Trentz O, Keel M (2003) Mcl-1 correlates with reduced apoptosis in neutrophils from patients with sepsis. J Am Coll Surg 197(6):964–973PubMedCrossRef
21.
go back to reference Goldshmit Y, McLenachan S, Turnley A (2006) Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Res Brain Res Rev 52(2):327–345CrossRef Goldshmit Y, McLenachan S, Turnley A (2006) Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Res Brain Res Rev 52(2):327–345CrossRef
22.
go back to reference Hildebrand F, Pape HC, Krettek C (2005) [The importance of cytokines in the posttraumatic inflammatory reaction]. Unfallchirurg 108(10):793–803PubMedCrossRef Hildebrand F, Pape HC, Krettek C (2005) [The importance of cytokines in the posttraumatic inflammatory reaction]. Unfallchirurg 108(10):793–803PubMedCrossRef
23.
go back to reference Kam PC, Ferch NI (2000) Apoptosis: mechanisms and clinical implications. Anaesthesia 55(11):1081–1093PubMedCrossRef Kam PC, Ferch NI (2000) Apoptosis: mechanisms and clinical implications. Anaesthesia 55(11):1081–1093PubMedCrossRef
24.
go back to reference Anton IM, Jones GE (2006) WIP: a multifunctional protein involved in actin cytoskeleton regulation. Eur J Cell Biol 85(3–4):295–304PubMedCrossRef Anton IM, Jones GE (2006) WIP: a multifunctional protein involved in actin cytoskeleton regulation. Eur J Cell Biol 85(3–4):295–304PubMedCrossRef
25.
go back to reference Jaffer ZM, Chernoff J (2002) p21-activated kinases: three more join the Pak. Int J Biochem Cell Biol 34(7):713–717PubMedCrossRef Jaffer ZM, Chernoff J (2002) p21-activated kinases: three more join the Pak. Int J Biochem Cell Biol 34(7):713–717PubMedCrossRef
Metadata
Title
Gene expression profiles are influenced by ISS, MOF, and clinical outcome in multiple injured patients: a genome-wide comparative analysis
Authors
V. Bogner
C. Kirchhoff
H. V. Baker
J. C. Stegmaier
L. L. Moldawer
W. Mutschler
P. Biberthaler
Publication date
01-05-2007
Publisher
Springer-Verlag
Published in
Langenbeck's Archives of Surgery / Issue 3/2007
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI
https://doi.org/10.1007/s00423-007-0182-5

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