Urine as a source for clinical proteome analysis: From discovery to clinical application |
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Authors: | Eva Rodrí guez-Suá rez,Justyna Siwy,Petra Zü rbig,Harald Mischak |
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Affiliation: | 1. Mosaiques Diagnostics GmbH, Hannover, Germany;2. Nephrology Department, Charité Hospital, Berlin, Germany;3. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom |
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Abstract: | The success of clinical proteome analysis should be assessed based on the clinical impact following implementation of findings. Although there have been several technological advancements in mass spectrometry in the last years, these have not resulted in similar advancements in clinical proteomics. In addition, application of proteomic biomarkers in clinical diagnostics and practical improvement in the disease management is extremely rare. In this review, we discuss the relevant issues associated with identification of robust biomarkers of clinical value. Urine appears to be an ideal source of biomarkers, for theoretical, methodological, and practical reasons. Therefore, this review is focused on the search for biomarkers in urine within the last decade. Urine can be used for non-invasive assessment of a variety of diseases including those affecting the urogenital tract and also other pathologies such as cardiovascular disease or appendicitis. We also discuss the importance of data validation, an essential step in translating biomarkers into the clinical practice. Furthermore, we examine several examples of apparently successful proteomic biomarker discovery studies and their implications for disease diagnosis, prognosis, and therapy evaluation. We also discuss some current challenges in this field and reflect on future research prospects. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. |
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Keywords: | 2DE, two dimensional electrophoresis AKI, acute kidney injury ANN, artificial neural networks ATN, acute tubular necrosis BPN, brain natriuretic peptide CAD, coronary artery disease CE&ndash MS, capillary electrophoresis coupled to mass spectrometry CKD, chronic kidney diseases CT, computed tomography DIGE, difference gel electrophoresis DN, diabetic nephropathy ECM, extracellular matrix ELISA, enzyme-linked immunosorbent assay EMA, European Medicines Agency EuroKUP, European Kidney and Urine Proteomics FDA, Food and Drug Administration GvHD, graft-versus-host-disease HF, heart failure HPLC, high pressure liquid chromatography HSCT, hematopoietic stem cell transplantation IgAN, immunoglobulin A nephropathy iTRAQ, isobaric tags for relative and absolute quantitation LC, liquid chromatography LRG, leucine-rich-2-glycoprotein LTQ-FT, linear ion trap quadrupole and Fourier transform LV, left ventricular MALDI, matrix-assisted laser desorption/ionization MI, myocardial infarction MS/MS, tandem mass spectrometry MS, mass spectrometry NIHSS, National Institutes of Health Stroke Scale PC, prostate cancer PSA, prostate-specific antigen PRA, perenal azotemia SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis SCr, serum creatinine SRM, selected reaction monitoring UPJ, ureteropelvic junction obstruction WB, western blot |
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