Glycan analysis of colorectal cancer samples reveals stage-dependent changes in CEA glycosylation patterns

Abstract

BackgroundCarcinoembryonic antigen (CEA) is a glycoprotein associated with colorectal cancer (CRC). While the functions of its gene and protein have been fully characterized, its post-translational modifications in the context of CRC development remain undefined.MethodsTo show the correlation between the different stages of CRC development and changes in the glycosylation patterns of CEA, we analyzed CEA in tumor tissues (CEA-T) and paired tumor-adjacent normal tissues (CEA-A) from 53 colorectal cancer patients using a high-density lectin microarray containing 56 plant lectins.ResultsWe detected higher expression levels of fucose, mannose and Thomsen–Friedenreich antigen, and lower expression levels of N-acetylgalactosamine, N-acetylglucosamine, galactose, branched and bisecting N-glycans on CEA in the tumor tissues relative to the tumor-adjacent normal tissues. Furthermore, a combinatorial assessment of 9 lectins is sufficient to distinguish CRC tumor tissues from tumor-adjacent normal tissues with 83% sensitivity and ~ 90% specificity. Moreover, the levels of N-acetylgalactosamine, mannose, galactose, N-acetylglucosamine on CEA showed a downward trend after first experiencing an increase at Stage II with the stages of CRC.ConclusionsOur insights into the changing CEA glycosylation patterns and their role in the development of CRC highlight the importance of glycan variants on CEA for early clinical detection and staging of CRC.Electronic supplementary materialThe online version of this article (10.1186/s12014-018-9182-4) contains supplementary material, which is available to authorized users.

N-Glycomic Signature of Stage II Colorectal Cancer and Its Association With the Tumor Microenvironment

“…Galactosylation was found to be decreased in lung cancer tissues and on the tumor-associated human carcinoma antigen (CEA) in CRC [19,62]. Zhao et al, hypothesized that the down-regulated galactosylation on CEA in tumor may be correlated with CRC immune response [19]. The stroma is largely orchestrated by inflammatory and immune cells, so the increased level of galactosylation in our study may be correlated to the inflammatory/immune response against cancer cells.…”

“…The interface stroma of the group with longer survival was characterized by an increase of galactosylation per antenna in the diantennary complex-types glycans. Galactosylation was found to be decreased in lung cancer tissues and on the tumor-associated human carcinoma antigen (CEA) in CRC [19,62]. Zhao et al, hypothesized that the down-regulated galactosylation on CEA in tumor may be correlated with CRC immune response [19].…”

“…Alterations in glycosylation patterns have been associated with the development and progression of various types of cancer [12,13]. In CRC, these glycomic changes have shown to be discriminative between normal and cancerous epithelial cell lines and potentially reflect tumor stage specificity [14][15][16][17][18][19]. However, it should be noted that the majority of studies on glycosylation changes in CRC were conducted using human serum samples or cell culture material.…”

The role of tissue and serum carcinoembryonic antigen in stages I to III of colorectal cancer—A retrospective cohort study

“…The CEA gene was recently classified as an immunoglobulin gene super family member . One recent research showed CEA was a glycoprotein associated with colorectal cancer (CRC) and the changing CEA glycosylation patterns and their role in the development of CRC highlight the importance of glycan variants on CEA for early clinical detection and staging of CRC …”

“…24 One recent research showed CEA was a glycoprotein associated with colorectal cancer (CRC) and the changing CEA glycosylation patterns and their role in the development of CRC highlight the importance of glycan variants on CEA for early clinical detection and staging of CRC. 25 CEA is a widely used tumor marker globally and can not only be detected in the blood of CRC patients but also in the tumor tissue. 26 The CEA gene and antibody expressions in tumor tissues have already been studied; however, studies on s-CEA and its prognostic value in CRC, locally and internationally, are relatively limited and are not comprehensive.…”