Mass spectrometry based proteomics in urine ...

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May 11, 2007 - Theodorescu D, Wittke S, Ross MM, Walden M, Conaway M, Just .... Jean-Charles Sanchez, Pierre-Alain Binz, Denis F.Hochstrasser,.

World J Urol DOI 10.1007/s00345-007-0206-3


Mass spectrometry based proteomics in urine biomarker discovery Dan Theodorescu · Harald Mischak

Received: 11 May 2007 / Accepted: 13 July 2007 © Springer-Verlag 2007

Abstract All organisms contain 1,000s of proteins and peptides in their body Xuids, which undergo disease-speciWc changes. Advances in the understanding of the functional relevance of these polypeptides under diVerent (patho)physiological conditions and the identiWcation of indicative changes with disease would greatly enhance diagnosis and therapy. The low-molecular-weight proteome, also termed peptidome, provides a rich source of information. Due to its lower molecular weight, the peptidome can be assessed without the need for sample manipulation like tryptic digests. This advantage facilitates comparative analysis but it also raises technical challenges diVering from those in proteomics. The Wrst part of this manuscript, is focused on the low-molecular-weight urinary proteome and reviews methodological aspects of sample collection, preparation, analysis, and data evaluation. The second part summarizes the recent progress in the deWnition and identiWcation of clinically relevant polypeptide markers.

Harald Mischak represents the UROSYSTEOMICS consortium. D. Theodorescu Department of Molecular Physiology, University of Virginia, Charlottesville, USA D. Theodorescu Department of Urology, University of Virginia, Charlottesville, USA D. Theodorescu Mellon Prostate Cancer Institute, University of Virginia, Charlottesville, USA H. Mischak (&) Mosaiques Diagnostics and Therapeutics AG, Mellendorfer Straße 7–9, 30625 Hannover, Germany e-mail: [email protected]

Keywords Urine · Biomarker · Proteomics · Mass spectromtery

Basic considerations A deeper knowledge of the functional relevance of proteins and peptides (polypeptides) in body Xuids under diVerent physiological and pathophysiological conditions is one of the main challenges in proteome research [1, 2]. Changes [both in the expression level and due to post-translational modiWcations (PTM)] may reXect normal physiological, but also pathological processes, highlighting the potential role of some polypeptides as biomarkers of speciWc diseases. These biomarkers have the potential to improve diagnosis of disease and monitoring the response to therapy, and may aid drug development. Since polypeptides in body Xuids are relatively easily accessible, these represent a target of major interest for diagnostic purposes. Among body Xuids, urine is especially attractive for biomarker discovery in urological disease for the following reasons: (1) Urine can be obtained in large quantities using noninvasive procedures. Consequently, ample material is available for analysis, assessment of reproducibility, and for optimization of analysis protocols. In addition, repeated sampling from the same individual is simple, facilitating longitudinal studies. (2) Urine generally contains proteins and peptides of lower molecular mass (

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