Display options
Share it on

Biomark Insights. 2007 Apr 19;2:155-64.

Ubiquitin fusion degradation protein 1 as a blood marker for the early diagnosis of ischemic stroke.

Biomarker insights

Laure Allard, Natacha Turck, Pierre R Burkhard, Nadia Walter, Anna Rosell, Marianne Gex-Fabry, Denis F Hochstrasser, Joan Montaner, Jean-Charles Sanchez

Affiliations

  1. Biomedical Proteomics Research Group, Department of Structural Biology and Bioinformatics, Medical University Center, CH-1211 Geneva 4, Switzerland.

PMID: 19662200 PMCID: PMC2717829

Abstract

BACKGROUND: Efficacy of thrombolysis in acute ischemic stroke is strongly related to physician's ability to make an accurate diagnosis and to intervene within 3-6 h after event onset. In this context, the discovery and validation of very early blood markers have recently become an urgent, yet unmet, goal of stroke research. Ubiquitin fusion degradation protein 1 is increased in human postmortem CSF, a model of global brain insult, suggesting that its measurement in blood may prove useful as a biomarker of stroke.

METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to measure UFD1 in plasma and sera in three independent cohorts, European (Swiss and Spanish) and North-American retrospective analysis encompassing a total of 123 consecutive stroke and 90 control subjects.

RESULTS: Highly significant increase of ubiquitin fusion degradation protein 1 (UFD1) was found in Swiss stroke patients with 71% sensitivity (95% CI, 52-85.8%), and 90% specificity (95% CI, 74.2-98%) (N = 31, p < 0.0001). Significantly elevated concentration of this marker was then validated in Spanish (N = 39, p < 0.0001, 95% sensitivity (95% CI, 82.7-99.4%)), 76% specificity (95% CI, 56.5-89.7%)) and North-American stroke patients (N = 53, 62% sensitivity (95% CI, 47.9-75.2%), 90% specificity (95% CI, 73.5-97.9%), p < 0.0001). Its concentration was increased within 3 h of stroke onset, on both the Swiss (p < 0.0001) and Spanish (p = 0.0004) cohorts.

CONCLUSIONS: UFD1 emerges as a reliable plasma biomarker for the early diagnosis of stroke, and in the future, might be used in conjunction with clinical assessments, neuroimaging and other blood markers.

Keywords: Brain Damage; Diagnosis; Plasma Markers; Stroke; UFD1

References

  1. J Neurochem. 1999 Feb;72(2):741-50 - PubMed
  2. Am J Med Genet. 2001 Aug 8;105(6):529-33 - PubMed
  3. Proteome Sci. 2004 Nov 18;2(1):7 - PubMed
  4. Stroke. 2001 Nov;32(11):2575-9 - PubMed
  5. Lancet. 2007 Jan 27;369(9558):249-50 - PubMed
  6. Biol Psychiatry. 1999 Oct 1;46(7):882-91 - PubMed
  7. Science. 1999 Feb 19;283(5405):1158-61 - PubMed
  8. Electrophoresis. 2004 Aug;25(15):2564-75 - PubMed
  9. Clin Chem. 2005 Nov;51(11):2043-51 - PubMed
  10. Hum Mol Genet. 1997 Feb;6(2):259-65 - PubMed
  11. Am J Med Genet. 1995 Oct 23;59(1):103-13 - PubMed
  12. BMC Neurol. 2004 Jan 15;4:2 - PubMed
  13. Neurobiol Aging. 2005 Feb;26(2):207-27 - PubMed
  14. Proteomics. 2003 Aug;3(8):1495-9 - PubMed
  15. Electrophoresis. 2004 Jul;25(14):2402-12 - PubMed
  16. Clin Chem. 2003 Oct;49(10):1733-9 - PubMed
  17. Stroke. 2001 Jan;32(1):133-8 - PubMed
  18. Clin Exp Immunol. 2004 Jul;137(1):117-22 - PubMed
  19. Stroke. 2000 Nov;31(11):2670-7 - PubMed
  20. J Am Geriatr Soc. 2004 Sep;52(9):1586-7 - PubMed
  21. Neurosci Lett. 2001 Jan 19;297(3):187-90 - PubMed
  22. Eur J Clin Invest. 1991 Oct;21(5):497-500 - PubMed
  23. Neuroreport. 2002 Apr 16;13(5):611-5 - PubMed
  24. Lancet. 2007 Jan 27;369(9558):293-8 - PubMed
  25. Stroke. 1987 Sep-Oct;18(5):911-8 - PubMed
  26. Brain Res Mol Brain Res. 2002 Dec 30;109(1-2):128-33 - PubMed
  27. Mol Cell Proteomics. 2004 Jan;3(1):66-72 - PubMed
  28. Neurol Sci. 2004 Feb;24(6):390-6 - PubMed
  29. Lancet. 2007 Jan 27;369(9558):319-30 - PubMed
  30. Mult Scler. 2004 Jun;10(3):245-60 - PubMed
  31. Trends Cell Biol. 2004 Dec;14(12):703-11 - PubMed
  32. Proteomics. 2004 Jul;4(7):2117-24 - PubMed
  33. Proteomics. 2004 Aug;4(8):2234-41 - PubMed
  34. Am J Hum Genet. 1992 May;50(5):924-33 - PubMed
  35. Stroke. 2004 Jan;35(1):57-63 - PubMed
  36. Eur Neurol. 2002;47(1):45-51 - PubMed
  37. Stroke. 2001 Aug;32(8):1759-66 - PubMed

Publication Types