Journal
ANALYTICAL CHEMISTRY
Volume 92, Issue 19, Pages 13361-13368Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.0c02704
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Funding
- NIH [R01 DK071801, R56MH110215, RF1AG052324, U01CA231081]
- University of Wisconsin Head and Neck SPORE grant [P50DE026787]
- NIH shared instrument grant [NIH-NCRR S10RR029531]
- University of Wisconsin-Madison, Office of the Vice Chancellor for Research and Graduate Education
- Wisconsin Alumni Research Foundation
- American Society for Mass Spectrometry
- University of Wisconsin-Madison School of Pharmacy
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Glycosylation is a major protein post-translational modification whose dysregulation has been associated with many diseases. Herein, an on-tissue chemical derivatization strategy based on positively charged hydrazine reagent (Girard's reagent P) coupled with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was developed for analysis of N-glycans from FFPE treated tissue sections. The performance of the proposed approach was evaluated by analysis of monosaccharides, oligosaccharides, N-glycans released from glycoproteins, as well as MS imaging of N-glycans from human cancer tissue sections. The results demonstrated that the signal-to-noise ratios for target saccharides were notably improved after chemical derivatization, in which signals were enhanced by 230-fold for glucose and over 28-fold for maltooctaose. Improved glycome coverage was obtained for N-glycans derived from glycoproteins and tissue samples after chemical derivatization. Furthermore, on-tissue derivatization was applied for MALDI-MSI of N-glycans from human laryngeal cancer and ovarian cancer tissues. Differentially expressed N-glycans among the tumor region, adjacent normal tissue region, and tumor proximal collagen stroma region were imaged, revealing that high-mannose type N-glycans were predominantly expressed in the tumor region. Overall, our results indicate that the on-tissue labeling strategy coupled with MALDI-MSI shows great potential to spatially characterize N-glycan expression within heterogeneous tissue samples with enhanced sensitivity. This study provides a promising approach to better understand the pathogenesis of cancer related aberrant glycosylation, which is beneficial to the design of improved clinical diagnosis and therapeutic strategies.
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