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.