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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 language | English |
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Article number | 1800482 |
Pages (from-to) | 1-11 |
Number of pages | 11 |
Journal | Proteomics |
Volume | 19 |
Issue number | 21-22 |
Early online date | 16 Aug 2019 |
DOIs | |
Publication status | Published - Nov 2019 |
Keywords
- formalin-fixed paraffin-embedded
- mass spectrometry imaging
- matrix-assisted laser desorption/ionization
- N-glycan
- ovarian cancer
- tissue
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ARC CoE Nanoscale BioPhotonics (CNBP) (RAAP)
Piper, J., Goldys, E., Packer, N. & Jin, D.
20/06/14 → …
Project: Research