MALDI mass spectrometry imaging of early- and late-stage serous ovarian cancer tissue reveals stage-specific N-glycans

Matthew T. Briggs, Mark R. Condina, Yin Ying Ho, Arun V. Everest-Dass, Parul Mittal, Gurjeet Kaur, Martin K. Oehler, Nicolle H. Packer, Peter Hoffmann*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Epithelial ovarian cancer is one of the most fatal gynecological malignancies in adult women. As studies on protein N-glycosylation have extensively reported aberrant patterns in the ovarian cancer tumor microenvironment, obtaining spatial information will uncover tumor-specific N-glycan alterations in ovarian cancer development and progression. matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is employed to investigate N-glycan distribution on formalin-fixed paraffin-embedded ovarian cancer tissue sections from early- and late-stage patients. Tumor-specific N-glycans are identified and structurally characterized by porous graphitized carbon-liquid chromatography-electrospray ionization-tandem mass spectrometry (PGC-LC-ESI-MS/MS), and then assigned to high-resolution images obtained from MALDI-MSI. Spatial distribution of 14 N-glycans is obtained by MALDI-MSI and 42 N-glycans (including structural and compositional isomers) identified and structurally characterized by LC-MS. The spatial distribution of oligomannose, complex neutral, bisecting, and sialylated N-glycan families are localized to the tumor regions of late-stage ovarian cancer patients relative to early-stage patients. Potential N-glycan diagnostic markers that emerge include the oligomannose structure, (Hex)6 + (Man)3(GlcNAc)2, and the complex neutral structure, (Hex)2 (HexNAc)2 (Deoxyhexose)1 + (Man)3(GlcNAc)2. The distribution of these markers is evaluated using a tissue microarray of early- and late-stage patients.

Original languageEnglish
Article number1800482
Pages (from-to)1-11
Number of pages11
JournalProteomics
Volume19
Issue number21-22
Early online date31 Jul 2019
DOIs
Publication statusPublished - Nov 2019

Keywords

  • formalin-fixed paraffin-embedded
  • mass spectrometry imaging
  • matrix-assisted laser desorption/ionization
  • N-glycan
  • ovarian cancer
  • tissue

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  • Projects

    ARC CoE Nanoscale BioPhotonics (CNBP) (RAAP)

    Piper, J., Goldys, E., Packer, N. & Jin, D.

    20/06/14 → …

    Project: Research

    Cite this

    Briggs, M. T., Condina, M. R., Ho, Y. Y., Everest-Dass, A. V., Mittal, P., Kaur, G., ... Hoffmann, P. (2019). MALDI mass spectrometry imaging of early- and late-stage serous ovarian cancer tissue reveals stage-specific N-glycans. Proteomics, 19(21-22), 1-11. [1800482]. https://doi.org/10.1002/pmic.201800482