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dc.contributor.authorGomes, Catarina
dc.contributor.authorAlmeida, Andreia
dc.contributor.authorBarreira, Ana
dc.contributor.authorCalheiros, Juliana
dc.contributor.authorPinto, Filipe
dc.contributor.authorAbrantes, Rafaela
dc.contributor.authorCosta, Ana
dc.contributor.authorPolonia, Antonio
dc.contributor.authorCampos, Diana
dc.contributor.authorOsorio, Hugo
dc.contributor.authorSousa, Hugo
dc.contributor.authorPinto-de-Sousa, Joao
dc.contributor.authorKolarich, Daniel
dc.contributor.authorReis, Celso A
dc.date.accessioned2019-12-12T03:24:04Z
dc.date.available2019-12-12T03:24:04Z
dc.date.issued2019
dc.identifier.issn1838-7640
dc.identifier.doi10.7150/thno.33858
dc.identifier.urihttp://hdl.handle.net/10072/389713
dc.description.abstractMalignant transformation of gastric cells is accompanied by the deregulated expression of glycosyltransferases leading to the biosynthesis of tumor-associated glycans such as the sialyl-Lewis X antigen (SLex). SLex presence on cell surface glycoconjugates increases the invasive capacity of gastric cancer cells and is associated with tumor metastasis. ST3Gal IV enzyme is involved in the synthesis of SLex antigen and overexpressed in gastric carcinomas. Herein, we identified the glycoproteins carrying SLex in gastric cancer cells overexpressing ST3Gal IV enzyme and evaluated their biomarker potential for gastric carcinoma. Methods: SLex modified glycoproteins were identified applying western blot and mass spectrometry. Immunoprecipitation, proximity ligation assay (PLA), E-selectin binding assay and CRISPR/cas9 knockout experiments were performed to characterize the presence of SLex on the identified glycoprotein. Protein N-glycans of the SLex protein carrier were in deep analyzed by porous-graphitized-carbon liquid-chromatography and tandem mass spectrometry glycomics. In silico expression analysis of α2-3 sialyltransferase ST3Gal IV and SLex protein carrier was performed and the conjoint expression of the SLex modified glycoproteins evaluated by immunohistochemistry and PLA in a series of gastric carcinomas. Results: Carcinoembryonic antigen (CEA; CEACAM5) was identified and validated by different methodologies as a major carrier of SLex. N-glycomics of CEA revealed that complex N-glycans are capped with α2-3 linked sialic acid (Neu5Acα2-3Galβ1-4GlcNAc). Data set analysis of ST3Gal IV and CEA showed that ST3Gal IV expression was associated with patient´s poor survival, whereas CEA did not show any prognostic value. The co-expression of both CEA and SLeX was observed in 86,3% of gastric carcinoma cases and 74,5% of the total cases displayed the conjoint CEA+SLex in situ PLA expression. This expression was associated with clinicopathological features of the tumors, including infiltrative pattern of tumor growth, presence of venous invasion and patient's poor survival. CEA immunoprecipitation from gastric carcinoma tissues also confirmed the presence of SLex. Conclusion: CEA is the major glycoprotein carrying SLex in gastric carcinoma and the conjoint detection of CEA-SLex is associated with aggressive tumor features highlighting its PLA detection as a biomarker of gastric cancer patient prognosis for theranostic applications.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherIvyspring International Publisher
dc.relation.ispartofpagefrom7431
dc.relation.ispartofpageto7446
dc.relation.ispartofissue24
dc.relation.ispartofjournalTheranostics
dc.relation.ispartofvolume9
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode1112
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsMedicine, Research & Experimental
dc.subject.keywordsResearch & Experimental Medicine
dc.subject.keywordsGastric Cancer
dc.titleCarcinoembryonic antigen carrying SLe(X) as a new biomarker of more aggressive gastric carcinomas
dc.typeJournal article
dc.type.descriptionC2 - Articles (Other)
dcterms.bibliographicCitationGomes, C; Almeida, A; Barreira, A; Calheiros, J; Pinto, F; Abrantes, R; Costa, A; Polonia, A; Campos, D; Osorio, H; Sousa, H; Pinto-de-Sousa, J; Kolarich, D; Reis, CA, Carcinoembryonic antigen carrying SLe(X) as a new biomarker of more aggressive gastric carcinomas, Theranostics, 2019, 9 (24), pp. 7431-7446
dcterms.dateAccepted2019-09-10
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2019-12-12T03:21:30Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorKolarich, Daniel
gro.griffith.authorFerreira de Almeida, Andreia F.


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