Approaching clinical proteomics: Current state and future fields of application in fluid proteomics

Rolf Apweiler, Charalampos Aslanidis, Thomas Deufel, Andreas Gerstner, Jens Hansen, Dennis Hochstrasser, Roland Kellner, Markus Kubicek, Friedrich Lottspeich, Edmund Maser, Hans Werner Mewes, Helmut E. Meyer, Stefan Müllner, Wolfgang Mutter, Michael Neumaier, Peter Nollau, Hans G. Nothwang, Fredrik Ponten, Andreas Radbruch, Knut ReinertGregor Rothe, Hannes Stockinger, Attila Tarnok, Mike J. Taussig, Andreas Thiel, Joachim Thiery, Marius Ueffing, Günther Valet, Joel Vandekerckhove, Wiltrud Verhuven, Christoph Wagener, Oswald Wagner, Gerd Schmitz

Research output: Contribution to journalReview articlepeer-review

117 Scopus citations

Abstract

The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics. The nature of the human body fluid proteome with its large dynamic range of protein concentrations presents problems with quantitation. The extreme complexity of the proteome in body fluids presents enormous challenges and requires the establishment of standard operating procedures for handling of specimens, increasing sensitivity for detection and bioinformatical tools for distribution of proteomic data into the public domain. From studies of in vitro diagnostics, especially in clinical chemistry, it is evident that most errors occur in the preanalytical phase and during implementation of the diagnostic strategy. This is also true for clinical proteomics, and especially for fluid proteomics because of the multiple pretreatment processes. These processes include depletion of high-abundance proteins from plasma or enrichment processes for urine where biological variation or differences in proteolytic activities in the sample along with preanalytical variables such as inter- and intra-assay variability will likely influence the results of proteomics studies. However, before proteomic analysis can be introduced at a broader level into the clinical setting, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement and data analysis needs to be improved. In this review, we discuss the recent technological advances and applications that fulfil the criteria for clinical proteomics, with the focus on fluid proteomics. These advances relate to preanalytical factors, analytical standardization and quality-control measures required for effective implementation into routine laboratory testing in order to generate clinically useful information. With new disease biomarker candidates, it will be crucial to design and perform clinical studies that can identify novel diagnostic strategies based on these techniques, and to validate their impact on clinical decision-making.

Original languageEnglish
Pages (from-to)724-744
Number of pages21
JournalClinical Chemistry and Laboratory Medicine
Volume47
Issue number6
DOIs
StatePublished - 1 Jun 2009
Externally publishedYes

Keywords

  • Cerebrospinal fluid (CSF)
  • Clinical proteomics
  • Fluid proteomics
  • Mass spectrometry (MS)
  • Matrix assisted laser desorption/ionization (MALDI)
  • Preanalytical effects
  • Standard operating procedures (SOP)
  • Surface-enhanced laser desorption/ionization (SELDI)

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