Carcinoembryonic antigen glycosylation: revealing novel features of human glycosylation and cancer origin specificity
Author(s)
Almeida, Andreia
Jacob, Francis
Stavenhagen, Kathrin
Alagesan, Kathrivel
Mischak, Michaela
Wuhrer, Manfred
Everest-Dass, Arunu
Reis, Celso A
Kolarich, Daniel
Year published
2020
Metadata
Show full item recordAbstract
Carcinoembryonic Antigen (CEA) is a biomarker strongly associated with tumour progression and metastasis. Even though N-glycans make up »50% of the entire CEA molecule, current knowledge on CEA specific glycosylation in health and disease is scarce. We show for the first time in an indepth glycomics and glycoproteomics study that the over 270 different N-glycans identified exhibited antenna fucosylation and sialylation features that allowed a clear CEA body origin assignment. Colon-derived CEA carried a hitherto not described, hexosylated bisected GlcNAc glycoepitope. All analysed CEAs contained a 29th site of N-glycosylation ...
View more >Carcinoembryonic Antigen (CEA) is a biomarker strongly associated with tumour progression and metastasis. Even though N-glycans make up »50% of the entire CEA molecule, current knowledge on CEA specific glycosylation in health and disease is scarce. We show for the first time in an indepth glycomics and glycoproteomics study that the over 270 different N-glycans identified exhibited antenna fucosylation and sialylation features that allowed a clear CEA body origin assignment. Colon-derived CEA carried a hitherto not described, hexosylated bisected GlcNAc glycoepitope. All analysed CEAs contained a 29th site of N-glycosylation on Asn71, located within a non-canonical 71N-R-Q73 sequence motif critical for CD8a binding. Correlation analyses of CEA and glycosyltransferase genes across the TGCA dataset revealed that CEACAM5 and B4GALNT3 expression levels were indicative for survival prediction. Our results open novel opportunities to understand CEA function, its role as a cancer marker but also reveal hitherto unknown aspects of glycobiology
View less >
View more >Carcinoembryonic Antigen (CEA) is a biomarker strongly associated with tumour progression and metastasis. Even though N-glycans make up »50% of the entire CEA molecule, current knowledge on CEA specific glycosylation in health and disease is scarce. We show for the first time in an indepth glycomics and glycoproteomics study that the over 270 different N-glycans identified exhibited antenna fucosylation and sialylation features that allowed a clear CEA body origin assignment. Colon-derived CEA carried a hitherto not described, hexosylated bisected GlcNAc glycoepitope. All analysed CEAs contained a 29th site of N-glycosylation on Asn71, located within a non-canonical 71N-R-Q73 sequence motif critical for CD8a binding. Correlation analyses of CEA and glycosyltransferase genes across the TGCA dataset revealed that CEACAM5 and B4GALNT3 expression levels were indicative for survival prediction. Our results open novel opportunities to understand CEA function, its role as a cancer marker but also reveal hitherto unknown aspects of glycobiology
View less >
Conference Title
Glycobiology
Volume
30
Issue
12
Subject
Biological sciences
Biomedical and clinical sciences
Clinical sciences
Oncology and carcinogenesis
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology