Carcinoembryonic antigen carrying SLe(X) as a new biomarker of more aggressive gastric carcinomas

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Gomes, C (Author) Other; Almeida, A (Author) Other; Barreira, A (Author) Other; Calheiros, J (Author) Other; Pinto, F (Author) Other; Abrantes, R (Author) Other; Costa, A (Author) Other; Polonia, A (Author) Other; Campos, D (Author) Other; Osorio, H (Author) Other; Sousa, H (Author) FMUP; Pinto de Sousa, J (Author) Other; Kolarich, D (Author) Other; Celso Reis (Author) ICBAS

Journal

The Journal is awaiting validation by the Administrative Services.

Title: THERANOSTICS

Vol. 9

Pages: 7431-7446

ISSN: 1838-7640

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 23 Citations

Other information

Authenticus ID: P-00R-5ZS

DOI: 10.7150/thno.33858

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16