2024-03-29T15:52:16Zhttps://dspace.library.uu.nl/oai/dareoai:dspace.library.uu.nl:1874/2021512024-02-23T14:12:50Zcom_1874_296827col_1874_296828dare
URN:NBN:NL:UI:10-1874-202151
2024-02-23T15:12:50.834Z
https://dspace.library.uu.nl/handle/1874/202151
Specific Investigation of Sample Handling Effects on Protease Activities and Absolute Serum Concentrations of Various Putative Peptidome Cancer Biomarkers
van den Broek
I.
aut
Sparidans
R.W.
aut
Schellens
J.H.M.
aut
Beijnen
J.H.
aut
Clinical Pharmacology
aut
NKI
aut
Population-based studies of drug treatment: from molecule to patient outcomes
aut
Programma Schellens/Beijnen (Geneesmiddelen Toxicologie)
aut
Dep Farmaceutische wetenschappen
aut
Sub Clinical Pharmacology
aut
text
info:eu-repo/semantics/Article
2010-09-30
en
Introduction In the search for novel cancer biomarkers, various proteolytically derived peptides have been proposed to exhibit cancer or cancer-type specificity. As these peptides are presumably also generated after sample collection by tumor-specific proteases, extensive investigation of the involved proteolytic processes is crucial for further research. Materials and Methods Using two previously developed and fully validated liquid-chromatography coupled to tandem-mass spectrometry assays, absolute quantification of, in total, 13 proteolytically derived peptides in human serum was accomplished. The analytes included eight peptides derived from inter-α-trypsin inhibitor heavy chain-4 (ITIH4-30, ITIH4-29, ITIH4-28, ITIH4-27, ITIH4-26, ITIH4-25, ITIH4-22, and ITIH4-21), bradykinin, des-Arg9-bradykinin, Hyp3-bradykinin, and fragments from fibrinogen-α-chain (Fib-α [605–629]) and complement component 4a (C4a [1337–1350]). Samples were obtained from different healthy individuals and prepared with variable tube types, clotting times, and temperatures. Furthermore, stabilities in the serum fraction were assessed and compared to stabilities in serum from breast cancer patients. Results and Discussion The quantitative analyses showed either increasing or decreasing serum concentrations during blood coagulation, while comparable effects were observed in serum separated from the blood clot. Furthermore, comparisons of inter- and intra-individual variations suggested better reflection of an individual’s protease activity after prolonged ex vivo incubation. This was illustrated for the putative breast cancer marker ITIH4-22, revealing better differentiation after incubation of serum at ambient temperature for 24 h. Conclusion The presented study provides suggestions for more specific and optimized sample preparation, as well as extended knowledge necessary to further explore the opportunities of these proteolytic peptides as cancer biomarkers.
Epidemiology
Farmacie(FARM)
Biomedische technologie en medicijnen
Ziekenhuisstructuur en organisatie van de gezondheidszorg
Public Health
Clinical Proteomics
BioMed Central
2010-09-30
1542-6416
6
115
10.1007/s12014-010-9054-z
1874/202151
2024-02-23T15:12:50.834Z
http://purl.org/eprint/accessRights/OpenAccess