title: Investigations on aberrant glycosylation of glycosphingolipids in colorectal cancer tissues using liquid chromatography and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS).
abstract: Cancer is a leading cause of death and alterations of glycosylation are characteristic features of malignant cells. Colorectal cancer is one of the most common cancers and its exact causes and biology are not yet well understood. Here, we compared glycosylation profiles of colorectal tumor tissues and corresponding control tissues of 13 colorectal cancer patients to contribute to the understanding of this cancer. Using MALDI-TOF(/TOF)-MS and 2-dimensional LC-MS/MS we characterized enzymatically released and 2-aminobenzoic acid labeled glycans from glycosphingolipids. Multivariate data analysis revealed significant differences between tumor and corresponding control tissues. Main discriminators were obtained, which represent the overall alteration in glycosylation of glycosphingolipids during colorectal cancer progression, and these were found to be characterized by (1) increased fucosylation, (2) decreased acetylation, (3) decreased sulfation, (4) reduced expression of globo-type glycans, as well as (5) disialyl gangliosides. The findings of our current research confirm former reports, and in addition expand the knowledge of glycosphingolipid glycosylation in colorectal cancer by revealing new glycans with discriminative power and characteristic, cancer-associated glycosylation alterations. The obtained discriminating glycans can contribute to progress the discovery of biomarkers to improve diagnostics and patient treatment.
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands;
authors.forename: Stephanie
authors.initials: S
authors.lastname: Holst
authors.forename: Kathrin
authors.initials: K
authors.lastname: Stavenhagen
authors.forename: Crina I A
authors.initials: CI
authors.lastname: Balog
authors.forename: Carolien A M
authors.initials: CA
authors.lastname: Koeleman
authors.forename: Liam M
authors.initials: LM
authors.lastname: McDonnell
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Mayboroda
authors.forename: Aswin
authors.initials: A
authors.lastname: Verhoeven
authors.forename: Wilma E
authors.initials: WE
authors.lastname: Mesker
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
authors.forename: Manfred
authors.initials: M
authors.lastname: Wuhrer
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D015394:Molecular Structure; D015999:Multivariate Analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D006028:Glycosphingolipids