Determination of peptides and proteins in human urine with capillary electrophoresis–mass spectrometry, a suitable tool for the establishment of new diagnostic markers

Wittke, Stefan; Fliser, Danilo; Haubitz, Marion; Bartel, Sebastian; Krebs, Ronald; Hausadel, Frank; Hillmann, Meike; Golovko, Igor; Koester, Peer; Haller, Hermann; Kaiser, Thorsten; Mischak, Harald; Weissinger, Eva M.

doi:10.1016/s0021-9673(03)00713-1

Cited by 184 publications

(166 citation statements)

References 36 publications

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“…In urine, 247 polypeptides have been identified that were present in urine of at least 50% healthy individuals [215]. Examination of patients with the same disease allowed relating polypeptide profile to specific disease, and to the stage of the disease.…”

Section: Urinary Proteinsmentioning

confidence: 99%

“…However, no single polypeptide was identified that would be characteristic for a specific disease and simultaneously absent in all control samples [207]. Urine of patients with kidney diseases provided 27 exclusive polypeptides and 13 others, present in control, were missing [122,212,215,216]. Similarly, CE-MS/MS was used to analyze urinary samples from 112 patients with type II diabetes.…”

Section: Urinary Proteinsmentioning

confidence: 99%

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Capillary electrophoresis of proteins 2003–2005

Dolnı́k¹

2006

Electrophoresis

139

117

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This review article with 304 references describes recent developments in CE of proteins, and covers the two years since the previous review (Hutterer, K., Dolník, V., Electrophoresis 2003, 24, 3998-4012) through Spring 2005. It covers topics related to CE of proteins, including modeling of the electrophoretic migration of proteins, sample pretreatment, wall coatings, improving separation, various forms of detection, special electrophoretic techniques such as affinity CE, CIEF, and applications of CE to the analysis of proteins in real-world samples including human body fluids, food and agricultural samples, protein pharmaceuticals, and recombinant protein preparations.

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Section: Urinary Proteinsmentioning

confidence: 99%

Section: Urinary Proteinsmentioning

confidence: 99%

Capillary electrophoresis of proteins 2003–2005

Dolnı́k¹

2006

Electrophoresis

139

117

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“…However, the data on crude urine samples allow judging the recovery in all steps during sample preparation. Based on such comparisons, an efficient method to remove unwanted substances in the samples appeared to be the use of anion-exchange [39] or RP material [40]. Since we found that larger polypeptides did not elute efficiently from RP-C18 columns, we decided to use RP-C2 columns.…”

Section: Sample Preparationmentioning

confidence: 99%

Capillary electrophoresis coupled to mass spectrometry for clinical diagnostic purposes

2005

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Capillary electrophoresis coupled to mass spectrometry for clinical diagnostic purposesThe introduction of fast, sensitive, and robust techniques for proteomic analysis into clinical practice represents a major step toward a new diagnostic approach of body fluids. In addition, proteomics emerges as a key technology for the discovery of disease biomarkers in various body fluids. However, even in relatively protein-deprived body fluids such as urine, the complexity and wide dynamic range of protein expression pose a considerable challenge to both separation and identification technologies. In the present review we discuss from a clinical point-of-view recent advances of the use of proteomics in clinical diagnosis as well as therapy evaluation. We focus on capillary electrophoresis coupled to mass spectrometry (CE-MS) and discuss CE-MS from an application point of view evaluating its merits and vices with regard to biomarker discovery. This review further presents examples of clinical applications of CE-MS for detection and identification of biomarkers in urine. IntroductionIt is well appreciated for centuries that body fluids contain information on the "internal" environment, i.e., the function of tissues and organs, which can be used as a gauge for the well being of the organism. Although this concept was created by Hippocrates more than 2000 years ago, standardized clinical laboratory tests were not developed before the 20th century. Moreover, a systematic discovery of biomarkers was made possible only with the discovery of antibodies and their use in immunological assays such as radioimmuno assay (RIA), ELISA, etc. Their increasing use enabled detection and quantification of distinct molecules -mainly peptides and proteins -in various body fluids. However, these techniques were limited by their requirement of prior knowledge of the molecule and a specific probe. New functional proteomic approaches appeared to circumvent these limitations. Spurred by advances in MS it was hoped that proteomics would allow the analysis of thousands of peptides and proteins in one sample [1][2][3][4][5][6], but several obstacles turned up soon. The high complexity and wide dynamic range of peptides in body fluids required pre-MS separation techniques that offer high resolution and could cope with a wide dynamic range of peptide concentrations [3]. Further, suitable software for interpretation of a vast number of generated MS spectra as well as comparison of the data was a major challenge [7].The approach towards solving most of these problems was to reduce data complexity, for example by arbitrarily collecting data on only a few polypeptides and also to reduce resolution of the analysis instrument. Both were accomplished with the surface-enhanced laser desorption/ionization (SELDI) technology -a complex solution of analytes was allowed to interact with an active surface (ion-exchange, hydro-

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“…[27] used MALDI-TOF MSbased peptides profiling to successfully distinguish prostate, bladder, and breast cancer patients from healthy persons. However, there were only several reports on the study of peptidome in urine [28][29][30][31]. The large number of small peptides in urine provided the potential for disease diagnosis of the kidney function [32,33], while the peptidome of urine was not explored in-depth.…”

Section: Introductionmentioning

confidence: 99%

“…Solid phase extraction (SPE) is currently the most commonly used method to extract the peptides from urine [28][29][30][31], and is mainly based on their hydrophobicity but has no size selectivity. Nanoporous materials have shown great promise for sample pretreatment of body fluid in recent years [17,34,35].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the human urine endogenous peptides by nanoparticle extraction and mass spectrometry identification

Yang

et al. 2014

Analytica Chimica Acta

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Determination of peptides and proteins in human urine with capillary electrophoresis–mass spectrometry, a suitable tool for the establishment of new diagnostic markers

Cited by 184 publications

References 36 publications

Capillary electrophoresis of proteins 2003–2005

Capillary electrophoresis of proteins 2003–2005

Capillary electrophoresis coupled to mass spectrometry for clinical diagnostic purposes

Analysis of the human urine endogenous peptides by nanoparticle extraction and mass spectrometry identification

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