Targeted Mass Spectrometry-Based Assays for Relative Quantification of 30 Brain-Related Proteins and Their Clinical Applications

被引:17
作者
Begcevic, Ilijana [1 ,2 ]
Brinc, Davor [1 ,2 ,3 ]
Dukic, Lora [4 ]
Simundic, Ana-Maria [4 ]
Zavoreo, Iris [5 ]
Kes, Vanja Basic [5 ]
Martinez-Morillo, Eduardo [6 ]
Batruch, Ihor [2 ]
Drabovich, Andrei P. [1 ,3 ]
Diamandis, Eleftherios P. [1 ,2 ,3 ]
机构
[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
[2] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5T 3L9, Canada
[3] Univ Hlth Network, Dept Clin Biochem, Toronto, ON M5G 2C4, Canada
[4] Univ Hosp Sveti Duh, Dept Med Lab Diagnost, Zagreb 10000, Croatia
[5] Univ Hosp Sestre Milosrdnice, Sch Med, Univ Dept Neurol, Zagreb 10000, Croatia
[6] Hosp Univ Cent Asturias, Dept Clin Biochem, Lab Med, Oviedo 33011, Spain
关键词
cerebrospinal fluid; mass spectrometry; selected reaction monitoring; biomarkers; multiple sclerosis; MULTIPLE-SCLEROSIS PATIENTS; MYELIN BASIC-PROTEIN; CEREBROSPINAL-FLUID; QUANTITATIVE PROTEOMICS; OSTEOPONTIN; BIOMARKERS; DISEASE; DIAGNOSIS; IDENTIFICATION; VALIDATION;
D O I
10.1021/acs.jproteome.7b00768
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Cerebrospinal fluid (CSF) is a promising clinical sample for identification of novel biomarkers for various neurological disorders. Considering its direct contact with brain tissue, CSF represents a valuable 'source of brain-related and brain-specific proteins. Multiple sclerosis is an inflammatory, demyelinating neurological disease affecting the central nervous system, and so far there are no diagnostic or prognostic disease specific biomarkers available in the clinic. The primary aim of the present study was to develop a targeted mass spectrometry assay for simultaneous quantification of 30 brain-related proteins in CSF and subsequently to demonstrate assay feasibility in neurological samples derived from multiple sclerosis patients. Our multiplex selected reaction monitoring assay had wide dynamic range (median fold range across peptides = 8.16 X 10(3)) and high assay reproducibility (median across peptides CV = 4%). Candidate biomarkers were quantified in CSF samples from neurologically healthy individuals (n = 9) and patients diagnosed with clinically isolated syndrome (n = 29) or early multiple sclerosis (n = 15).
引用
收藏
页码:2282 / 2292
页数:11
相关论文
共 42 条
[1]   Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma [J].
Addona, Terri A. ;
Abbatiello, Susan E. ;
Schilling, Birgit ;
Skates, Steven J. ;
Mani, D. R. ;
Bunk, David M. ;
Spiegelman, Clifford H. ;
Zimmerman, Lisa J. ;
Ham, Amy-Joan L. ;
Keshishian, Hasmik ;
Hall, Steven C. ;
Allen, Simon ;
Blackman, Ronald K. ;
Borchers, Christoph H. ;
Buck, Charles ;
Cardasis, Helene L. ;
Cusack, Michael P. ;
Dodder, Nathan G. ;
Gibson, Bradford W. ;
Held, Jason M. ;
Hiltke, Tara ;
Jackson, Angela ;
Johansen, Eric B. ;
Kinsinger, Christopher R. ;
Li, Jing ;
Mesri, Mehdi ;
Neubert, Thomas A. ;
Niles, Richard K. ;
Pulsipher, Trenton C. ;
Ransohoff, David ;
Rodriguez, Henry ;
Rudnick, Paul A. ;
Smith, Derek ;
Tabb, David L. ;
Tegeler, Tony J. ;
Variyath, Asokan M. ;
Vega-Montoto, Lorenzo J. ;
Wahlander, Asa ;
Waldemarson, Sofia ;
Wang, Mu ;
Whiteaker, Jeffrey R. ;
Zhao, Lei ;
Anderson, N. Leigh ;
Fisher, Susan J. ;
Liebler, Daniel C. ;
Paulovich, Amanda G. ;
Regnier, Fred E. ;
Tempst, Paul ;
Carr, Steven A. .
NATURE BIOTECHNOLOGY, 2009, 27 (07) :633-U85
[2]   CEREBROSPINAL-FLUID IN THE DIAGNOSIS OF MULTIPLE-SCLEROSIS - A CONSENSUS REPORT [J].
ANDERSSON, M ;
ALVAREZCERMENO, J ;
BERNARDI, G ;
COGATO, I ;
FREDMAN, P ;
FREDERIKSEN, J ;
FREDRIKSON, S ;
GALLO, P ;
GRIMALDI, LM ;
GRONNING, M ;
KEIR, G ;
LAMERS, K ;
LINK, H ;
MAGALHAES, A ;
MASSARO, AR ;
OHMAN, S ;
REIBER, H ;
RONNBACK, L ;
SCHLUEP, M ;
SCHULLER, E ;
SINDIC, CJM ;
THOMPSON, EJ ;
TROJANO, M ;
WURSTER, U .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1994, 57 (08) :897-902
[3]  
[Anonymous], 1991, PURE APPL CHEM, V63, P301
[4]   Identification of brain-enriched proteins in the cerebrospinal fluid proteome by LC-MS/MS profiling and mining of the Human Protein Atlas [J].
Begcevic, Ilijana ;
Brinc, Davor ;
Drabovich, Andrei P. ;
Batruch, Ihor ;
Diamandis, Eleftherios P. .
CLINICAL PROTEOMICS, 2016, 13
[5]   Cerebrospinal fluid and plasma biomarkers in Alzheimer disease [J].
Blennow, Kaj ;
Hampel, Harald ;
Weiner, Michael ;
Zetterberg, Henrik .
NATURE REVIEWS NEUROLOGY, 2010, 6 (03) :131-144
[6]   Osteopontin concentrations are increased in cerebrospinal fluid during attacks of multiple sclerosis [J].
Bornsen, Lars ;
Khademi, Mohsen ;
Olsson, Tomas ;
Sorensen, Per Soelberg ;
Sellebjerg, Finn .
MULTIPLE SCLEROSIS JOURNAL, 2011, 17 (01) :32-42
[7]   Increased osteopontin levels in the cerebrospinal fluid of patients with multiple sclerosis [J].
Braitch, Manjit ;
Nunan, Robert ;
Niepel, Graham ;
Edwards, Laura J. ;
Constantinescu, Cris S. .
ARCHIVES OF NEUROLOGY, 2008, 65 (05) :633-635
[8]   Validation of semaphorin 7A and ala-β-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis [J].
Canto, Ester ;
Tintore, Mar ;
Maria Villar, Luisa ;
Borras, Eva ;
Carlos Alvarez-Cermeno, Jose ;
Chiva, Cristina ;
Sabido, Eduard ;
Rovira, Alex ;
Montalban, Xavier ;
Comabella, Manuel .
JOURNAL OF NEUROINFLAMMATION, 2014, 11
[9]   The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease [J].
Chabas, D ;
Baranzini, SE ;
Mitchell, D ;
Bernard, CCA ;
Rittling, SR ;
Denhardt, DT ;
Sobel, RA ;
Lock, C ;
Karpuj, M ;
Pedotti, R ;
Heller, R ;
Oksenberg, JR ;
Steinman, L .
SCIENCE, 2001, 294 (5547) :1731-1735
[10]   Body fluid biomarkers in multiple sclerosis [J].
Comabella, Manuel ;
Montalban, Xavier .
LANCET NEUROLOGY, 2014, 13 (01) :113-126