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  Carcinoembryonic antigen carrying SLeX as a new biomarker of more aggressive gastric carcinomas

Gomes, C., Almeida, A., Barreira, A., Calheiros, J., Pinto, F., Abrantes, R., et al. (2019). Carcinoembryonic antigen carrying SLeX as a new biomarker of more aggressive gastric carcinomas. Theranostics, 9(24), 7431-7446. doi:10.7150/thno.33858.

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 Urheber:
Gomes, Catarina, Autor
Almeida, Andreia1, Autor           
Barreira, Ana, Autor
Calheiros, Juliana, Autor
Pinto, Filipe, Autor
Abrantes, Rafaela, Autor
Costa, Ana, Autor
Polonia, Antonio, Autor
Campos, Diana, Autor
Osorio, Hugo, Autor
Sousa, Hugo, Autor
Pinto-de-Sousa, Joao, Autor
Kolarich, Daniel1, Autor           
Reis, Celso A., Autor
Affiliations:
1Daniel Kolarich, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863301              

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Schlagwörter: Gastric Cancer; Carcinoembryonic antigen; Glycosylation; ST3Gal IV; Sialyl-Lewis X
 Zusammenfassung: Malignant 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 (SLe(x)). SLe(x) 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 SLe(x) antigen and overexpressed in gastric carcinomas.
Herein, we identified the glycoproteins carrying SLe(x) in gastric
cancer cells overexpressing ST3Gal IV enzyme and evaluated their
biomarker potential for gastric carcinoma.
Methods: SLe(x) 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 SLe(x) on the
identified glycoprotein. Protein N-glycans of the SLe(x) protein carrier
were in deep analyzed by porous-graphitized-carbon liquid-chromatography
and tandem mass spectrometry glycomics. In silico expression analysis of
alpha 2-3 sialyltransferase ST3Gal IV and SLe(x) protein carrier was
performed and the conjoint expression of the SLe(x) 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 SLe(x).
N-glycomics of CEA revealed that complex N-glycans are capped with alpha
2-3 linked sialic acid (Neu5Aca2-3Gal beta 1-4GlcNAc). 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 SLe(x) in gastric
carcinoma and the conjoint detection of CEA-SLe(x) is associated with
aggressive tumor features highlighting its PLA detection as a biomarker
of gastric cancer patient prognosis for theranostic applications.

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 Datum: 2019-10-112019
 Publikationsstatus: Erschienen
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 Art der Begutachtung: -
 Identifikatoren: DOI: 10.7150/thno.33858
ISI: 000489762100004
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Titel: Theranostics
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: Lake Haven, NSW 2263, Australia : Ivyspring int. publ.
Seiten: - Band / Heft: 9 (24) Artikelnummer: - Start- / Endseite: 7431 - 7446 Identifikator: ISSN: 1838-7640