title: Urine proteome analysis as a discovery tool in patients with deep vein thrombosis and pulmonary embolism.
abstract: Early and accurate detection of deep vein thrombosis (DVT) is an important clinical need. Based on the hypothesis that urinary peptides may hold information on DVT in conjunction with pulmonary embolism (PE), the study was aimed at identifying such peptide biomarkers using capillary electrophoresis coupled mass spectrometry.
  
  
  
  Patients with symptoms of unprovoked/idiopathic DVT and/or PE were examined by doppler-sonography or angio-computed tomography. Urinary proteome analysis allowed for identification of respective peptide biomarkers. To confirm their biological relevance, we induced PE in mice and assessed human ex vivo thrombi.
  
  
  
  We identified 62 urinary peptides as DVT-specific biomarkers, i.e. fragments of collagen type I and a fragment of fibrinogen β-chain. The presence of fibrinogen α/β in the acute thrombus, and collagen type I and osteopontin in the older, organized thrombus was demonstrated. The classifier DVT62 established through support vector machine (SVM) modeling based on the 62 identified peptides was validated in an independent cohort of 47 subjects (six cases and 41 controls) with a sensitivity of 100% and specificity of 83%.
  
  
  
  Urine proteome analysis enabled the detection of DVT-specific peptides, which were validated in human and mouse tissue. Furthermore, it allowed for the establishment of an urinary-proteome based classifier that is relatively specific for DVT. The data provide the basis for assessment of these biomarkers in a prospective clinical study.
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: von Zur Mühlen
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Koeck
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Schiffer
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Sackmann
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Zürbig
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Hilgendorf
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Reinöhl
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rivera
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zirlik
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hehrlein
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.|BHF Glasgow Cardiovascular Research, University of Glasgow, UK.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D024042:Collagen Type I / Q000235:genetics / Q000652:urine*; D019075:Electrophoresis, Capillary; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000652:urine*; D015870:Gene Expression; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D053495:Osteopontin / Q000235:genetics / Q000652:urine*; D020543:Proteome / Q000378:metabolism*; D011655:Pulmonary Embolism / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D012680:Sensitivity and Specificity; D060388:Support Vector Machine; D016482:Urinalysis / Q000295:instrumentation / Q000379:methods; D020246:Venous Thrombosis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000652:urine
chemical_list: C115499:BBeta fibrinogen; D015415:Biomarkers; D024042:Collagen Type I; D020543:Proteome; C506895:SPP1 protein, human; D053495:Osteopontin; D005340:Fibrinogen
keywords: Biomarker; Discovery Tool; Pulmonary Embolism; Thrombosis