title: Human gliosarcoma-associated ganglioside composition is complex and distinctive as evidenced by high-performance mass spectrometric determination and structural characterization.
abstract: Gangliosides (GGs), involved in malignant alteration and tumor progression/invasiveness, are considered as tumor biomarkers or therapeutic targets. Here, we describe the first systematic GG composition characterization in human gliosarcoma versus normal brain tissue using our recently developed mass spectrometry (MS) methods, based on nano-electrospray (nano-ESI), Fourier-transform ion cyclotron resonance (FT-ICR), and chip nano-ESI quadrupole time-of-flight (QTOF), complemented by thin-layer chromatographic (TLC) analysis and quantification. Combined MS enabled detection and structural assignment of 73 distinct GG species: many more than reported so far for investigated gliomas. Apart from the 7.4-times lower total GG content, gliosarcoma contained all major brain-associated species, however, in very altered proportions, exhibiting a highly distinctive pattern: GD3 (48.9%)>GD1a/nLD1>GD2/GT3>GM3>GT1b>GM2>GM1a/GM1b/nLM1>LM1>GD1b>GQ1b. MS also revealed abundant O-Ac-GD3; its sequencing provided structural evidence to postulate a novel O-Ac-GD3 isomer O-acetylated at the inner Neu5Ac-residue, previously not structurally confirmed. The high sensitivity and mass accuracy permitted the assignment of unusual minor species: GM4, Hex-HexNAc-nLM1, Gal-GD1, Fuc-GT1, GalNAc-GT1, O-Ac-GM3, di- O-Ac-GD3O-Ac-GD3, and O-Ac-GT3, not previously reported as glioma-associated. The gliosarcoma-expressed GA2 might represent a marker distinguishing astrocytic from oligodendroglial tumors. This is, to our knowledge, so far the most complete GG composition characterization of certain glioma, which demonstrates that our MS-based approach could provide essential structural information relevant to glycosphingolipid role(s) in brain tumor biology, differential diagnosis/prognosis and novel treatment concepts.
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Medicine, University of Zagreb, and Department of Neurology, Clinical Hospital Dubrava, Zagreb, Croatia.
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Vukelić
authors.forename: Svjetlana
authors.initials: S
authors.lastname: Kalanj-Bognar
authors.forename: Martin
authors.initials: M
authors.lastname: Froesch
authors.forename: Laura
authors.initials: L
authors.lastname: Bîndila
authors.forename: Boris
authors.initials: B
authors.lastname: Radić
authors.forename: Mark
authors.initials: M
authors.lastname: Allen
authors.forename: Jasna
authors.initials: J
authors.lastname: Peter-Katalinić
authors.forename: Alina D
authors.initials: AD
authors.lastname: Zamfir
mesh_terms: D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000378:metabolism; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003937:Diagnosis, Differential; D005732:Gangliosides / Q000032:analysis* / Q000378:metabolism; D018316:Gliosarcoma / Q000737:chemistry* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009836:Oligodendroglia / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D014408:Biomarkers, Tumor; D005732:Gangliosides