Peptide profiling of cerebrospinal fluid by mass spectrometry

Dekker, Lennard J. M.; Burgers, Peter C.; Kros, Johan M.; Luider, Theo M.

doi:10.1586/14789450.3.3.297

Cited by 14 publications

(12 citation statements)

References 80 publications

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“…Yet another advantage is the very high sensitivity and reproducibility of FTMS (11), which is higher than that of any other mass spectrometric techniques currently available. In addition, FTMS provides an excellent signal-to-noise ratio because the source of noise in MALDI-FTMS is of physical origin and is not a chemical-based noise as that generated in MALDI-TOF (24). These advantages allow the study of very small numbers of targeted cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of Glioma Neovascularization-related Proteins by Using MALDI-FTMS and Nano-LC Fractionation to Microdissected Tumor Vessels

Mustafa¹,

Burgers

Dekker

et al. 2007

Molecular & Cellular Proteomics

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The identification of angiogenesis-related proteins is important for the development of new antiangiogenic therapies, and such proteins are potential new biomarkers for gliomas. The aim of this study was to identify proteins that are exclusively present in glioma neovasculature and not in the vasculature of normal brain. We combined advanced proteomics techniques to compare the expression profiles of microdissected blood vessels from glioma with blood vessels of normal control brain samples. We measured the enzymatic generated peptide profiles from these microdissected samples by MALDI-FTMS. Subsequently, the samples were fractionated by nano-LC prior to MALDI-TOF/TOF. This combined approach enabled us to identify four proteins that appeared to be exclusively expressed in the glioma blood vessels. Two of these proteins, fibronectin and colligin 2, were validated on tissue sections using specific antibodies. We found that both proteins are present in active angiogenesis in glioma, other neoplasms, and reactive conditions in which neoangiogenesis takes place. This work proves that gel-free mass spectrometric techniques can be used on relatively

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Section: Discussionmentioning

confidence: 99%

Identification of Glioma Neovascularization-related Proteins by Using MALDI-FTMS and Nano-LC Fractionation to Microdissected Tumor Vessels

Mustafa¹,

Burgers

Dekker

et al. 2007

Molecular & Cellular Proteomics

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“…Standardized sample handling is also important when trying to compare results between different laboratories (12)(13)(14). In the search for molecular biomarkers related to disorders of the central nervous system, CSF is the most promising biofluid because of its close contact to the affected tissue (13,(15)(16)(17)(18)(19)(20).…”

confidence: 99%

The Impact of Delayed Storage on the Measured Proteome and Metabolome of Human Cerebrospinal Fluid

et al. 2011

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BACKGROUND Because cerebrospinal fluid (CSF) is in close contact with diseased areas in neurological disorders, it is an important source of material in the search for molecular biomarkers. However, sample handling for CSF collected from patients in a clinical setting might not always be adequate for use in proteomics and metabolomics studies. METHODS We left CSF for 0, 30, and 120 min at room temperature immediately after sample collection and centrifugation/removal of cells. At 2 laboratories CSF proteomes were subjected to tryptic digestion and analyzed by use of nano-liquid chromatography (LC) Orbitrap mass spectrometry (MS) and chipLC quadrupole TOF-MS. Metabolome analysis was performed at 3 laboratories by NMR, GC-MS, and LC-MS. Targeted analyses of cystatin C and albumin were performed by LC–tandem MS in the selected reaction monitoring mode. RESULTS We did not find significant changes in the measured proteome and metabolome of CSF stored at room temperature after centrifugation, except for 2 peptides and 1 metabolite, 2,3,4-trihydroxybutanoic (threonic) acid, of 5780 identified peptides and 93 identified metabolites. A sensitive protein stability marker, cystatin C, was not affected. CONCLUSIONS The measured proteome and metabolome of centrifuged human CSF is stable at room temperature for up to 2 hours. We cannot exclude, however, that changes undetectable with our current methodology, such as denaturation or proteolysis, might occur because of sample handling conditions. The stability we observed gives laboratory personnel at the collection site sufficient time to aliquot samples before freezing and storage at −80 °C.

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“…Furthermore, the general protein concentration in CSF (0.2-0.5 g/l) is much lower than in plasma/serum (60-80 g/l). 22 As most classical biomarkers have been identified among the low-abundant proteins, 23 it is necessary to fractionate and/or deplete the high-abundant circulating proteins that otherwise might mask proteins of low concentrations. It has been shown that fractionation can give up to a tenfold increase in the number of proteins identified.…”

Section: Protein Biomarker Discoverymentioning

confidence: 99%

Clinical perspectives of high‐resolution mass spectrometry–based proteomics in neuroscience—Exemplified in amyotrophic lateral sclerosis biomarker discovery research

2008

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Biomarker discovery is a central application in today's proteomic research. There is an urgent need for valid biomarkers to improve diagnostic tools and treatment in many disorders, such as the rapidly progressing neurodegenerative disorder amyotrophic lateral sclerosis (ALS) that has a fatal outcome in about 3 years and yet no curative treatment. Screening for clinically relevant biomarkers puts high demands on high-throughput, rapid and precise proteomic techniques. There is a large variety in the methods of choice involving mainly gel-based approaches as well as chromatographic techniques for multi-dimensional protein and peptide separations followed by mass spectrometry (MS) analysis. This special feature article will discuss some important aspects of MS-based clinical proteomics and biomarker discovery in the field of neurodegenerative diseases and ALS research respectively, with the aim to provide a prospective view on current and future research aspects in the field. Furthermore, examples for application of high-resolution MS-based proteomic strategies for ALS biomarker discovery will be demonstrated with two studies previously reported by our group. These studies include among others, utilization of capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS) for advanced protein pattern classification in cerebrospinal fluid (CSF) samples of ALS patients as well as highly sensitive protein identification in minimal amounts of postmortem spinal cord tissue and laser micro-dissected motor neurons using FT-ICR-MS in conjunction with nanoflow LC coupled to matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (LC-MALDI-TOF-TOF-MS).

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Peptide profiling of cerebrospinal fluid by mass spectrometry

Cited by 14 publications

References 80 publications

Identification of Glioma Neovascularization-related Proteins by Using MALDI-FTMS and Nano-LC Fractionation to Microdissected Tumor Vessels

Identification of Glioma Neovascularization-related Proteins by Using MALDI-FTMS and Nano-LC Fractionation to Microdissected Tumor Vessels

The Impact of Delayed Storage on the Measured Proteome and Metabolome of Human Cerebrospinal Fluid

Clinical perspectives of high‐resolution mass spectrometry–based proteomics in neuroscience—Exemplified in amyotrophic lateral sclerosis biomarker discovery research

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