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

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) MS(2)-MS(4.) 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 MS(2)-MS(4) 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.