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

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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.

Ganglioside isomer discrimination in human astrocytoma by Orbitrap multistage MS

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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

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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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Correspondence to Alina D. Zamfir or Corina Flangea.

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Zamfir, A.D., Fabris, D., Capitan, F. et al. Profiling and sequence analysis of gangliosides in human astrocytoma by high-resolution mass spectrometry. Anal Bioanal Chem 405, 7321–7335 (2013). https://doi.org/10.1007/s00216-013-7173-x

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  • DOI: https://doi.org/10.1007/s00216-013-7173-x

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