title: High-throughput and targeted in-depth mass spectrometry-based approaches for biofluid profiling and biomarker discovery.
abstract: Proteomics aims to create a link between genomic information, biological function and disease through global studies of protein expression, modification and protein-protein interactions. Recent advances in key proteomics tools, such as mass spectrometry (MS) and (bio)informatics, provide tremendous opportunities for biomarker-related clinical applications. In this review, we focus on two complementary MS-based approaches with high potential for the discovery of biomarker patterns and low-abundant candidate biomarkers in biofluids: high-throughput matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy-based methods for peptidome profiling and label-free liquid chromatography-based methods coupled to MS for in-depth profiling of biofluids with a focus on subproteomes, including the low-molecular-weight proteome, carrier-bound proteome and N-linked glycoproteome. The two approaches differ in their aims, throughput and sensitivity. We discuss recent progress and challenges in the analysis of plasma/serum and proximal fluids using these strategies and highlight the potential of liquid chromatography-MS-based proteomics of cancer cell and tumor secretomes for the discovery of candidate blood-based biomarkers. Strategies for candidate validation are also described.
authors.affiliation: OncoProteomics Laboratory, Department of Medical Oncology, VUmc Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. c.jimenez@vumc.nl
authors.forename: Connie R
authors.initials: CR
authors.lastname: Jimenez
authors.forename: Sander
authors.initials: S
authors.lastname: Piersma
authors.forename: Thang V
authors.initials: TV
authors.lastname: Pham