Native glycan fragments detected by MALDI-FT-ICR mass spectrometry imaging impact gastric cancer biology and patient outcome
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Thomas Kunzke1, Benjamin Balluff2, Annette Feuchtinger1, Achim Buck1, Rupert Langer3, Birgit Luber4, Florian Lordick5, Horst Zitzelsberger6, Michaela Aichler1 and Axel Walch1
1Research Unit Analytical Pathology, Helmholtz Zentrum München, Oberschleißheim, Germany
2Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands
3Institute of Pathology, University of Bern, Bern, Switzerland
4Institute of Pathology, Technische Universität München, Munich, Germany
5University Cancer Center Leipzig, University Clinic Leipzig, Leipzig, Germany
6Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Oberschleißheim, Germany
Axel Walch, email: [email protected]
Keywords: glycans, gastric cancer, formalin-fixed paraffin-embedded tissue, MALDI, mass spectrometry imaging
Received: September 14, 2016 Accepted: June 02, 2017 Published: July 10, 2017
Glycosylation in cancer is a highly dynamic process that has a significant impact on tumor biology. Further, the attachment of aberrant glycan forms is already considered a hallmark of the disease state. Mass spectrometry has become a prominent approach to analyzing glycoconjugates. Specifically, matrix-assisted laser desorption/ionisation -mass spectrometric imaging (MALDI-MSI) is a powerful technique that combines mass spectrometry with histology and enables the spatially resolved and label-free detection of glycans. The most common approach to the analysis of glycans is the use of mass spectrometry adjunct to PNGase F digestion and other chemical reactions. In the current study, we perform the analysis of formalin-fixed, paraffin-embedded (FFPE) tissues for natively occurring bioactive glycan fragments without prior digestion or chemical reactions using MALDI-FT-ICR-MSI. We examined 106 primary resected gastric cancer patient tissues in a tissue microarray and correlated native-occurring fragments with clinical endpoints, therapeutic targets such as epidermal growth factor receptor (EGFR) and HER2/neu expressions and the proliferation marker MIB1. The detection of a glycosaminoglycan fragment in tumor stroma regions was determined to be an independent prognostic factor for gastric cancer patients. Native glycan fragments were significantly linked to the expression of EGFR, HER2/neu and MIB1. In conclusion, we are the first to report the in situ detection of native-occurring bioactive glycan fragments in FFPE tissues that influence patient outcomes. These findings highlight the significance of glycan fragments in gastric cancer tumor biology and patient outcome.
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