Oral Presentation 23rd Annual Lorne Proteomics Symposium 2018

MALDI mass spectrometry imaging of early- and late-stage serous ovarian cancer tissue reveals stage-specific N-glycans (#37)

Matthew Briggs 1 2 , Yin Ying Ho 1 , Mark Condina 2 , Arun Everest-Dass 3 4 , Gurjeet Kaur 5 , Martin Oehler 6 , Nicolle Packer 3 4 , Peter Hoffmann 1 2
  1. Adelaide Proteomics Centre, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA
  2. Future Industries Institute, The University of South Australia, Mawson Lakes, SA, Australia
  3. Faculty of Science, Biomolecular Frontiers Research Centre, Macquarie University, Sydney, NSW
  4. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia
  5. Institute for Research in Molecular Medicine, Universiti Sains , Pulau Pinang, Malaysia
  6. Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia

Epithelial ovarian cancer is one of the most fatal gynaecological malignancies in adult women with an estimated 1,580 new cases diagnosed and 1,047 deaths estimated in Australia during 2017. N-glycomic studies have extensively reported aberrant patterns in the ovarian cancer tumour microenvironment. Therefore, obtaining spatial information is essential to uncover tumour-specific N-glycan alterations in ovarian cancer development and progression. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) was employed to investigate the spatial distribution of N-glycans on formalin-fixed paraffin-embedded (FFPE) ovarian cancer tissue sections from both early-stage (n = 3) and late-stage (n = 3) patients. Tumour-specific N-glycans were identified and structurally characterised by PGC-LC-ESI-MS/MS, and then assigned to high-resolution images obtained from MALDI-MSI. A total of 14 N-glycans were visualised as ion intensity maps while 42 N-glycans (including structural and compositional isomers) were identified and structurally characterised. The spatial distribution of high mannose, complex neutral, bisecting and sialylated N-glycan families were only observed to be localised to the tumour regions of late-stage ovarian cancer patients relative to early-stage patients. Potential N-glycans diagnostic markers that emerged include the high mannose structure, (Hex)6 + (Man)3(GlcNAc)2, the bisecting structure, (Hex)1 (HexNAc)3 (Deoxyhexose)1 + (Man)3(GlcNAc)2, and the sialylated structure, (Hex)2 (HexNAc)2 (NeuAc)1 + (Man)3(GlcNAc)2. These observations require validation on large patient cohorts, by utilising tissue microarrays (TMAs) as well as evaluation of specific glyco-gene expression levels.            

  1. Matthew T Briggs, Yin Ying Ho, Gurjeet Kaur, Martin K Oehler, Arun V Everest-Dass, Nicolle H Packer, Peter Hoffmann: N-glycan matrix-assisted laser desorption/ionization mass spectrometry imaging protocol for formalin-fixed paraffin-embedded tissues. Rapid Communications in Mass Spectrometry 03/2017;, DOI:10.1002/rcm.7845
  2. Arun V. Everest-Dass, Matthew T. Briggs, Gurjeet Kaur, Martin K. Oehler, Peter Hoffmann, Nicolle H Packer: N -Glycan MALDI Imaging Mass Spectrometry on Formalin-Fixed Paraffin-Embedded Tissue Enables the Delineation of Ovarian Cancer Tissues. Molecular & Cellular Proteomics 07/2016; 15(9):mcp.M116.059816., DOI:10.1074/mcp.M116.059816
  3. Ove J R Gustafsson, Matthew T Briggs, Mark R Condina, Lyron J Winderbaum, Matthias Pelzing, Shaun R McColl, Arun V Everest-Dass, Nicolle H Packer, Peter Hoffmann: MALDI imaging mass spectrometry of N-linked glycans on formalin-fixed paraffin-embedded murine kidney. Analytical and Bioanalytical Chemistry 12/2014; 407(8)., DOI:10.1007/s00216-014-8293-7