In Situ <i>N</i>-Glycosylation Signatures of Epithelial Ovarian Cancer Tissue as Defined by MALDI Mass Spectrometry Imaging
The particularly high mortality of epithelial ovarian cancer (EOC) is in part linked to limited understanding of its molecular signatures. Although there are data available on in situ <i>N</i>-glycosylation in EOC tissue, previous studies focused primarily on neutral <i>N</i>...
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MDPI AG
2022-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/4/1021 |
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| author | Marta Grzeski Eliane T. Taube Elena I. Braicu Jalid Sehouli Véronique Blanchard Oliver Klein |
| author_facet | Marta Grzeski Eliane T. Taube Elena I. Braicu Jalid Sehouli Véronique Blanchard Oliver Klein |
| author_sort | Marta Grzeski |
| collection | DOAJ |
| description | The particularly high mortality of epithelial ovarian cancer (EOC) is in part linked to limited understanding of its molecular signatures. Although there are data available on in situ <i>N</i>-glycosylation in EOC tissue, previous studies focused primarily on neutral <i>N</i>-glycan species and, hence, still little is known regarding EOC tissue-specific sialylation. In this proof-of-concept study, we implemented MALDI mass spectrometry imaging (MALDI-MSI) in combination with sialic acid derivatization to simultaneously investigate neutral and sialylated <i>N</i>-glycans in formalin-fixed paraffin-embedded tissue microarray specimens of less common EOC histotypes and non-malignant borderline ovarian tumor (BOT). The applied protocol allowed detecting over 50 <i>m/z</i> species, many of which showed differential tissue distribution. Most importantly, it could be demonstrated that α2,6- and α2,3-sialylated <i>N</i>-glycans are enriched in tissue regions corresponding to tumor and adjacent tumor-stroma, respectively. Interestingly, analogous <i>N</i>-glycosylation patterns were observed in tissue cores of BOT, suggesting that regio-specific <i>N</i>-glycan distribution might occur already in non-malignant ovarian pathologies. All in all, our data provide proof that the combination of MALDI-MSI and sialic acid derivatization is suitable for delineating regio-specific <i>N</i>-glycan distribution in EOC and BOT tissues and might serve as a promising strategy for future glycosylation-based biomarker discovery studies. |
| first_indexed | 2024-03-09T22:22:46Z |
| format | Article |
| id | doaj.art-073daa919c744bbca261e09e0421922c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:22:46Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-073daa919c744bbca261e09e0421922c2023-11-23T19:10:10ZengMDPI AGCancers2072-66942022-02-01144102110.3390/cancers14041021In Situ <i>N</i>-Glycosylation Signatures of Epithelial Ovarian Cancer Tissue as Defined by MALDI Mass Spectrometry ImagingMarta Grzeski0Eliane T. Taube1Elena I. Braicu2Jalid Sehouli3Véronique Blanchard4Oliver Klein5Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, GermanyInstitute of Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, GermanyDepartment of Gynecology, European Competence Center for Ovarian Cancer, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, GermanyDepartment of Gynecology, European Competence Center for Ovarian Cancer, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, GermanyInstitute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, GermanyBIH Center for Regenerative Therapies, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, GermanyThe particularly high mortality of epithelial ovarian cancer (EOC) is in part linked to limited understanding of its molecular signatures. Although there are data available on in situ <i>N</i>-glycosylation in EOC tissue, previous studies focused primarily on neutral <i>N</i>-glycan species and, hence, still little is known regarding EOC tissue-specific sialylation. In this proof-of-concept study, we implemented MALDI mass spectrometry imaging (MALDI-MSI) in combination with sialic acid derivatization to simultaneously investigate neutral and sialylated <i>N</i>-glycans in formalin-fixed paraffin-embedded tissue microarray specimens of less common EOC histotypes and non-malignant borderline ovarian tumor (BOT). The applied protocol allowed detecting over 50 <i>m/z</i> species, many of which showed differential tissue distribution. Most importantly, it could be demonstrated that α2,6- and α2,3-sialylated <i>N</i>-glycans are enriched in tissue regions corresponding to tumor and adjacent tumor-stroma, respectively. Interestingly, analogous <i>N</i>-glycosylation patterns were observed in tissue cores of BOT, suggesting that regio-specific <i>N</i>-glycan distribution might occur already in non-malignant ovarian pathologies. All in all, our data provide proof that the combination of MALDI-MSI and sialic acid derivatization is suitable for delineating regio-specific <i>N</i>-glycan distribution in EOC and BOT tissues and might serve as a promising strategy for future glycosylation-based biomarker discovery studies.https://www.mdpi.com/2072-6694/14/4/1021in situ <i>N</i>-glycosylationsialylationovarian cancerEOCimagingMALDI-MSI |
| spellingShingle | Marta Grzeski Eliane T. Taube Elena I. Braicu Jalid Sehouli Véronique Blanchard Oliver Klein In Situ <i>N</i>-Glycosylation Signatures of Epithelial Ovarian Cancer Tissue as Defined by MALDI Mass Spectrometry Imaging Cancers in situ <i>N</i>-glycosylation sialylation ovarian cancer EOC imaging MALDI-MSI |
| title | In Situ <i>N</i>-Glycosylation Signatures of Epithelial Ovarian Cancer Tissue as Defined by MALDI Mass Spectrometry Imaging |
| title_full | In Situ <i>N</i>-Glycosylation Signatures of Epithelial Ovarian Cancer Tissue as Defined by MALDI Mass Spectrometry Imaging |
| title_fullStr | In Situ <i>N</i>-Glycosylation Signatures of Epithelial Ovarian Cancer Tissue as Defined by MALDI Mass Spectrometry Imaging |
| title_full_unstemmed | In Situ <i>N</i>-Glycosylation Signatures of Epithelial Ovarian Cancer Tissue as Defined by MALDI Mass Spectrometry Imaging |
| title_short | In Situ <i>N</i>-Glycosylation Signatures of Epithelial Ovarian Cancer Tissue as Defined by MALDI Mass Spectrometry Imaging |
| title_sort | in situ i n i glycosylation signatures of epithelial ovarian cancer tissue as defined by maldi mass spectrometry imaging |
| topic | in situ <i>N</i>-glycosylation sialylation ovarian cancer EOC imaging MALDI-MSI |
| url | https://www.mdpi.com/2072-6694/14/4/1021 |
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