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https://hdl.handle.net/2440/102460
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dc.contributor.author | Everest-Dass, A. | - |
dc.contributor.author | Briggs, M. | - |
dc.contributor.author | Kaur, G. | - |
dc.contributor.author | Oehler, M. | - |
dc.contributor.author | Hoffmann, P. | - |
dc.contributor.author | Packer, N. | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Molecular and Cellular Proteomics, 2016; 15(9):3003-3016 | - |
dc.identifier.issn | 1535-9476 | - |
dc.identifier.issn | 1535-9484 | - |
dc.identifier.uri | http://hdl.handle.net/2440/102460 | - |
dc.description.abstract | Ovarian cancer is a fatal gynaecological malignancy in adult women with a five-year overall survival rate of only 30%. Glycomic and glycoproteomic profiling studies have reported extensive protein glycosylation pattern alterations in ovarian cancer. Therefore, spatio-temporal investigation of these glycosylation changes may unearth tissue-specific changes that occur in the development and progression of ovarian cancer. A novel method for investigating tissue-specific N-linked glycans is using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) on formalin-fixed paraffin-embedded (FFPE) tissue sections that can spatially profile N-glycan compositions released from proteins in tissue-specific regions. In this study, tissue regions of interest (e.g. tumor, stroma, adipose tissue and necrotic areas) were isolated from FFPE tissue sections of advanced serous ovarian cancers (n = 3). PGC-LC-ESI-MS/MS and MALDI-MSI were used as complementary techniques to firstly generate structural information on the tissue-specific glycans in order to then obtain high resolution images of the glycan structure distribution in ovarian cancer tissue. The N-linked glycan repertoires carried by the proteins in these tissue regions were structurally characterized for the first time in FFPE ovarian cancer tissue regions, using enzymatic peptide-N-glycosidase F (PNGase F) release of N-glycans. The released glycans were analyzed by porous graphitized carbon liquid chromatography (PGC-LC) and collision induced electrospray negative mode MS fragmentation analysis. The N-glycan profiles identified by this analysis were then used to determine the location and distribution of each N-glycan on FFPE ovarian cancer sections that were treated with PNGase F using high resolution MALDI-MSI. A tissue-specific distribution of N-glycan structures identified particular regions of the ovarian cancer sections. For example, high mannose glycans were predominantly expressed in the tumor tissue region whereas complex/hybrid N-glycans were significantly abundant in the intervening stroma. Therefore, tumor and non-tumor tissue regions were clearly demarcated solely on their N-glycan structure distributions. | - |
dc.description.statementofresponsibility | Arun V. Everest-Dass, Matthew T. Briggs, Gurjeet Kaur, Martin K. Oehler, Peter Hoffmann and Nicolle H. Packer | - |
dc.language.iso | en | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.rights | © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. | - |
dc.source.uri | http://www.mcponline.org/content/15/9/3003 | - |
dc.subject | Humans | - |
dc.subject | Ovarian Neoplasms | - |
dc.subject | Polysaccharides | - |
dc.subject | Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization | - |
dc.subject | Paraffin Embedding | - |
dc.subject | Tissue Fixation | - |
dc.subject | Proteomics | - |
dc.subject | Organ Specificity | - |
dc.subject | Female | - |
dc.subject | Glycomics | - |
dc.title | N-glycan MALDI imaging mass spectrometry on formalin-fixed paraffin-embedded tissue enables the delineation of ovarian cancer tissues | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1074/mcp.M116.059816 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/LP110100693 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/CE140100003 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Oehler, M. [0000-0002-2651-5913] | - |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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