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Proteomics. 2019 Jul 31:e1800482. doi: 10.1002/pmic.201800482. [Epub ahead of print]

MALDI Mass Spectrometry Imaging of Early- and Late-Stage Serous Ovarian Cancer Tissue Reveals Stage-Specific N-Glycans.

Author information

1
Future Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, SA, 5095, Australia.
2
Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide, SA, 5005, Australia.
3
Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, 4215, Australia.
4
ARC Centre for Nanoscale BioPhotonics (CNBP), Macquarie University, Sydney, NSW, 2109, Australia.
5
Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Pulau Pinang, 16150, Malaysia.
6
Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia.
7
Robinson Institute, University of Adelaide, Adelaide, SA, 5005, Australia.

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.

KEYWORDS:

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

PMID:
31364262
DOI:
10.1002/pmic.201800482

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