PuSH - Publikationsserver des Helmholtz Zentrums München: Native glycan fragments detected by MALDI-FT-ICR mass spectrometry imaging impact gastric cancer biology and patient outcome.

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Kunzke, T. ; Balluff, B.* ; Feuchtinger, A. ; Buck, A. ; Langer, R.* ; Luber, B.* ; Lordick, F.* ; Zitzelsberger, H. ; Aichler, M. ; Walch, A.K.

Native glycan fragments detected by MALDI-FT-ICR mass spectrometry imaging impact gastric cancer biology and patient outcome.

Oncotarget 8, 68012-68025 (2017)

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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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