Urinary proteomic biomarkers in coronary artery disease

Lukas U Zimmerli, Eric Schiffer, Petra Zürbig, David M Good, Markus Kellmann, Laetitia Mouls, Andrew R Pitt, Joshua J Coon, Roland E Schmieder, Karlheinz H Peter, Harald Mischak, Walter Kolch, Christian Delles, Anna F Dominiczak

Research output: Contribution to journalArticle

Abstract

Urinary proteomics is emerging as a powerful non-invasive tool for diagnosis and monitoring of variety of human diseases. We tested whether signatures of urinary polypeptides can contribute to the existing biomarkers for coronary artery disease (CAD). We examined a total of 359 urine samples from 88 patients with severe CAD and 282 controls. Spot urine was analyzed using capillary electrophoresis on-line coupled to ESI-TOF-MS enabling characterization of more than 1000 polypeptides per sample. In a first step a "training set" for biomarker definition was created. Multiple biomarker patterns clearly distinguished healthy controls from CAD patients, and we extracted 15 peptides that define a characteristic CAD signature panel. In a second step, the ability of the CAD-specific panel to predict the presence of CAD was evaluated in a blinded study using a "test set." The signature panel showed sensitivity of 98% (95% confidence interval, 88.7-99.6) and 83% specificity (95% confidence interval, 51.6-97.4). Furthermore the peptide pattern significantly changed toward the healthy signature correlating with the level of physical activity after therapeutic intervention. Our results show that urinary proteomics can identify CAD patients with high confidence and might also play a role in monitoring the effects of therapeutic interventions. The workflow is amenable to clinical routine testing suggesting that non-invasive proteomics analysis can become a valuable addition to other biomarkers used in cardiovascular risk assessment.
LanguageEnglish
Pages290-8
Number of pages9
JournalMolecular and Cellular Proteomics
Volume7
Issue number2
DOIs
Publication statusPublished - 1 Feb 2008

Fingerprint

Biomarkers
Proteomics
Coronary Artery Disease
Peptides
Urine
Confidence Intervals
Workflow
Capillary electrophoresis
Capillary Electrophoresis
Therapeutic Uses
Monitoring
Risk assessment
Exercise
Testing

Keywords

  • amino acid sequence
  • biological markers
  • Body Mass Index
  • case-control studies
  • coronary artery disease
  • female
  • humans
  • male
  • mass spectrometry
  • middle aged
  • molecular sequence data
  • peptides
  • proteome
  • ROC curve

Cite this

Zimmerli, L. U., Schiffer, E., Zürbig, P., Good, D. M., Kellmann, M., Mouls, L., ... Dominiczak, A. F. (2008). Urinary proteomic biomarkers in coronary artery disease. Molecular and Cellular Proteomics , 7(2), 290-8. https://doi.org/10.1074/mcp.M700394-MCP200
Zimmerli, Lukas U ; Schiffer, Eric ; Zürbig, Petra ; Good, David M ; Kellmann, Markus ; Mouls, Laetitia ; Pitt, Andrew R ; Coon, Joshua J ; Schmieder, Roland E ; Peter, Karlheinz H ; Mischak, Harald ; Kolch, Walter ; Delles, Christian ; Dominiczak, Anna F. / Urinary proteomic biomarkers in coronary artery disease. In: Molecular and Cellular Proteomics . 2008 ; Vol. 7, No. 2. pp. 290-8.
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Zimmerli, LU, Schiffer, E, Zürbig, P, Good, DM, Kellmann, M, Mouls, L, Pitt, AR, Coon, JJ, Schmieder, RE, Peter, KH, Mischak, H, Kolch, W, Delles, C & Dominiczak, AF 2008, 'Urinary proteomic biomarkers in coronary artery disease' Molecular and Cellular Proteomics , vol. 7, no. 2, pp. 290-8. https://doi.org/10.1074/mcp.M700394-MCP200

Urinary proteomic biomarkers in coronary artery disease. / Zimmerli, Lukas U; Schiffer, Eric; Zürbig, Petra; Good, David M; Kellmann, Markus; Mouls, Laetitia; Pitt, Andrew R; Coon, Joshua J; Schmieder, Roland E; Peter, Karlheinz H; Mischak, Harald; Kolch, Walter; Delles, Christian; Dominiczak, Anna F.

In: Molecular and Cellular Proteomics , Vol. 7, No. 2, 01.02.2008, p. 290-8.

Research output: Contribution to journalArticle

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T1 - Urinary proteomic biomarkers in coronary artery disease

AU - Zimmerli, Lukas U

AU - Schiffer, Eric

AU - Zürbig, Petra

AU - Good, David M

AU - Kellmann, Markus

AU - Mouls, Laetitia

AU - Pitt, Andrew R

AU - Coon, Joshua J

AU - Schmieder, Roland E

AU - Peter, Karlheinz H

AU - Mischak, Harald

AU - Kolch, Walter

AU - Delles, Christian

AU - Dominiczak, Anna F

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N2 - Urinary proteomics is emerging as a powerful non-invasive tool for diagnosis and monitoring of variety of human diseases. We tested whether signatures of urinary polypeptides can contribute to the existing biomarkers for coronary artery disease (CAD). We examined a total of 359 urine samples from 88 patients with severe CAD and 282 controls. Spot urine was analyzed using capillary electrophoresis on-line coupled to ESI-TOF-MS enabling characterization of more than 1000 polypeptides per sample. In a first step a "training set" for biomarker definition was created. Multiple biomarker patterns clearly distinguished healthy controls from CAD patients, and we extracted 15 peptides that define a characteristic CAD signature panel. In a second step, the ability of the CAD-specific panel to predict the presence of CAD was evaluated in a blinded study using a "test set." The signature panel showed sensitivity of 98% (95% confidence interval, 88.7-99.6) and 83% specificity (95% confidence interval, 51.6-97.4). Furthermore the peptide pattern significantly changed toward the healthy signature correlating with the level of physical activity after therapeutic intervention. Our results show that urinary proteomics can identify CAD patients with high confidence and might also play a role in monitoring the effects of therapeutic interventions. The workflow is amenable to clinical routine testing suggesting that non-invasive proteomics analysis can become a valuable addition to other biomarkers used in cardiovascular risk assessment.

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KW - molecular sequence data

KW - peptides

KW - proteome

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Zimmerli LU, Schiffer E, Zürbig P, Good DM, Kellmann M, Mouls L et al. Urinary proteomic biomarkers in coronary artery disease. Molecular and Cellular Proteomics . 2008 Feb 1;7(2):290-8. https://doi.org/10.1074/mcp.M700394-MCP200