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Urine as a source for clinical proteome analysis: From discovery to clinical application
Authors:Eva Rodríguez-Suárez  Justyna Siwy  Petra Zürbig  Harald Mischak
Institution: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
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.
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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