Mass spectrometry based biomarker discovery, verification, and validation - Quality assurance and control of protein biomarker assays

In its early years, mass spectrometry (MS)-based proteomics focused on the cataloging of proteins found in different species or different tissues. By 2005, proteomics was being used for protein quantitation, typically based on proteotypic peptides which act as surrogates for the parent proteins. Biomarker discovery is usually done by non-targeted shotgun proteomics, using relative quantitation methods to determine protein expression changes that correlate with disease (output given as up-or-down regulation or fold-increases). MS-based techniques can also perform absolute quantitation which is required for clinical applications (output given as protein concentrations). Here we describe the differences between these methods, factors that affect the precision and accuracy of the results, and some examples of recent studies using MS-based proteomics to verify cancer-related biomarkers. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.