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Analytical and Bioanalytical Chemistry

, Volume 405, Issue 23, pp 7321–7335 | Cite as

Profiling and sequence analysis of gangliosides in human astrocytoma by high-resolution mass spectrometry

  • Alina D. ZamfirEmail author
  • Dragana Fabris
  • Florina Capitan
  • Cristian Munteanu
  • Željka Vukelić
  • Corina FlangeaEmail author
Research Paper

Abstract

In this preliminary investigation, a low-grade astrocytoma (AcT) is investigated by high-resolution (HR) mass spectrometry (MS) aiming at characterization of gangliosides with potential biomarker value. The research was conducted towards a comparative mapping of ganglioside expression in AcT, its surrounding tissue (ST) and a normal control brain tissue (NT). HR MS was conducted in the negative ion mode nanoelectrospray ionization (nanoESI). Fragmentation analysis was carried out by collision-induced dissociation (CID) MS2–MS4. Due to the high resolving power and mass accuracy, by comparative mapping of the ganglioside extracts from AcT, ST and NT, under identical conditions, 37 different species in AcT, 40 in ST and 56 in NT were identified. AcT and ST were found to contain 18 identical ganglioside components. Among all three specimens, ST extract presented the highest levels of sialylation, fucosylation and acetylation, a feature which might be correlated to the tumor expansion in the adjacent brain area. MS mapping indicated also that AcT, ST and NT share one doubly deprotonated molecule at m/z 1063.31, attributable to GT1(d18:1/18:0) or GT1(d18:0/18:1). CID MS2–MS4 on these particular ions detected in AcT and ST provided data supporting GT1c isomer in the investigated astrocytoma tissue. Our results show that HR MS has a remarkable potential in brain cancer research for the determination of tumor-associated markers and for their structural determination.

Figure

Ganglioside isomer discrimination in human astrocytoma by Orbitrap multistage MS

Keywords

Astrocytoma High-resolution mass spectrometry Gangliosides Biomarker Screening and sequencing 

Abbreviations

AcT

Astrocytoma

CE

Capillary electrophoresis

Cer

Ceramide

CID

Collision-induced dissociation

ESI

Electrospray ionization

Fuc

Fucose

Gal

Galactose

GalNAc

N-acetylgalactosamine

Glc

Glucose

GlcNAc

N-acetylglucosamine

HCT

High-capacity ion trap

HPLC

High-performance liquid chromatography

HPTLC

High-performance thin layer chromatography

HR

High resolution

LC

Liquid chromatography

LCB

Long chain base

MALDI

Matrix-assisted laser desorption/ionization

MS

Mass spectrometry

MS/MS

Tandem mass spectrometry

MSn

Multistage mass spectrometry

NanoESI

Nanoelectrospray ionization

Neu5Ac

N-acetyl neuraminic acid

NT

Normal brain tissue

QTOF

Quadrupole time-of-flight

ST

Surrounding tissue

TIC

Total ion chromatogram

TLC

Thin layer chromatography

WHO

World Health Organization

Notes

Acknowledgments

This work was supported by the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, projects PN-II-ID-PCE-2011-3-0047, PN-II-PCCA-2011-142, PN-II-RU-TE-2011-2-0008 and FP7 Marie Curie-PIRSES-GA-2010-269256.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Alina D. Zamfir
    • 1
    • 2
    Email author
  • Dragana Fabris
    • 3
  • Florina Capitan
    • 1
  • Cristian Munteanu
    • 4
  • Željka Vukelić
    • 3
  • Corina Flangea
    • 1
    • 4
    Email author
  1. 1.Department of Chemical and Biological Sciences“Aurel Vlaicu” University of AradAradRomania
  2. 2.Mass Spectrometry LaboratoryNational Institute for Research and Development in Electrochemistry and Condensed MatterTimisoaraRomania
  3. 3.Department of Chemistry and Biochemistry, Faculty of MedicineUniversity of ZagrebZagrebCroatia
  4. 4.Department of Molecular and Cell BiologyBiochemistry Institute of the Romanian AcademyBucharestRomania

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