Clinical applications of capillary electrophoresis coupled to mass spectrometry in biomarker discovery: Focus on bladder cancer

Abstract

A major requirement in the application of proteins as clinical biomarkers is that they provide a highly sensitive and specific result in disease assessment. Since single biomarkers are generally of limited accuracy, a group or panel of well characterized biomarkers appears appropriate, providing a more robust and sensitive mass-spectrometry-based analytical platform. Capillary electrophoresis coupled to MS has been successfully used in biomarker discovery and application, as it enables the selective detection of peptides and small proteins, combining the high separation capacity of CE with the advanced sensitivity of MS. CE-MS allows the characterization of highly complex samples (such as urine, plasma and other biofluids) in a consistent and reproducible way. It has a range of applications, many focusing especially in studies on urinary peptide biomarkers in kidney and cardiovascular diseases. Another major field of interest has been malignancy of the genitourinary system. In the first part of this review we cover technical aspects and performance characteristics of CE-MS, with special focus on the requirements for biomarker discovery and clinical application. In the second part, we review the potential and development of CE-MS in the management of genitourinary cancers, especially bladder cancer (BCa). CE-MS has been employed in several studies aimed at discovering biomarkers for BCa that may be useful in diagnosis, monitoring for recurrence, and prediction of the risk for the muscle-invasive stage. In the last part of the review we discuss current challenges and provide an outlook for ongoing and possible future developments.

Proteomic Analysis of Vitreous Humor in Retinal Vein Occlusion

“…CE-MS is a powerful and very reproducible technology platform with known performance characteristics [ 25 ] and therefore is used as one of the most advanced techniques for the discovery of new protein biomarkers of clinical significance [ 25 – 28 ]. Furthermore, CE-MS allows the characterization of highly complex samples in a consistent and reproducible way and has a high reproducibility allowing the comparison of the protein content of samples over time [ 25 , 29 ]. LC-MS/MS was used in this study to provide sequence information (i.e.…”

Recent developments in capillary and microchip electroseparations of peptides (2013–middle 2015)

“…This fact, together with the ultrasmall injected sample volume (nL to pL), makes CE and CEC powerful and highly acknowledged methods in biomedical research and practice , where often only minute volumes from biopsy or dialysis samples are available, and in the single cell analysis . Detection and identification of particular peptides in complex biomatrices is of great importance also in peptidome/proteome analysis of biological fluids (blood, serum, plasma, CSF, urine, saliva), which could result in the discovery of new specific peptide biomarkers applicable in diagnosis and therapy of some diseases .…”

Recent developments and applications of capillary and microchip electrophoresis in proteomic and peptidomic analyses

“…Proteome analysis using CE–MS has been used in several clinical applications in the past years . The main focus of CE–MS‐based studies has been on the investigation of urine, due to the stability of the urinary proteome, ease of collection, and the low molecular mass of the present proteins and peptides, which can be analyzed without excessive manipulation, even without tryptic digestion .…”