dc.contributor.author | Sethi, Manveen K. | |
dc.contributor.author | Kim, Hoguen | |
dc.contributor.author | Park, Cheol Keun | |
dc.contributor.author | Baker, Mark S. | |
dc.contributor.author | Paik, Young-Ki | |
dc.contributor.author | Packer, Nicolle H. | |
dc.contributor.author | Hancock, William S. | |
dc.contributor.author | Fanayan, Susan | |
dc.contributor.author | Thaysen-Andersen, Morten | |
dc.date.accessioned | 2017-10-31T12:31:39Z | |
dc.date.available | 2017-10-31T12:31:39Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 0959-6658 | |
dc.identifier.doi | 10.1093/glycob/cwv042 | |
dc.identifier.uri | http://hdl.handle.net/10072/336514 | |
dc.description.abstract | Glycomics may assist in uncovering the structure–function relationships of protein glycosylation and identify glycoprotein markers in colorectal cancer (CRC) research. Herein, we performed label-free quantitative glycomics on a carbon-liquid chromatography–tandem mass spectrometry-based analytical platform to accurately profile the N-glycosylation changes associated with CRC malignancy. N-Glycome profiling was performed on isolated membrane proteomes of paired tumorigenic and adjacent non-tumorigenic colon tissues from a cohort of five males (62.6 ± 13.1 y.o.) suffering from colorectal adenocarcinoma. The CRC tissues were typed according to their epidermal growth factor receptor (EGFR) status by western blotting and immunohistochemistry. Detailed N-glycan characterization and relative quantitation identified an extensive structural heterogeneity with a total of 91 N-glycans. CRC-specific N-glycosylation phenotypes were observed including an overrepresentation of high mannose, hybrid and paucimannosidic type N-glycans and an under-representation of complex N-glycans (P < 0.05). Sialylation, in particular α2,6-sialylation, was significantly higher in CRC tumors relative to non-tumorigenic tissues, whereas α2,3-sialylation was down-regulated (P < 0.05). CRC stage-specific N-glycosylation was detected by high α2,3-sialylation and low bisecting β1,4-GlcNAcylation and Lewis-type fucosylation in mid-late relative to early stage CRC. Interestingly, a novel link between the EGFR status and the N-glycosylation was identified using hierarchical clustering of the N-glycome profiles. EGFR-specific N-glycan signatures included high bisecting β1,4-GlcNAcylation and low α2,3-sialylation (both P < 0.05) relative to EGFR-negative CRC tissues. This is the first study to correlate CRC stage and EGFR status with specific N-glycan features, thus advancing our understanding of the mechanisms causing the biomolecular deregulation associated with CRC. | |
dc.description.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Oxford University Press | |
dc.relation.ispartofpagefrom | 1064 | |
dc.relation.ispartofpageto | 1078 | |
dc.relation.ispartofissue | 10 | |
dc.relation.ispartofjournal | Glycobiology | |
dc.relation.ispartofvolume | 25 | |
dc.subject.fieldofresearch | Biological sciences | |
dc.subject.fieldofresearch | Biochemistry and cell biology not elsewhere classified | |
dc.subject.fieldofresearch | Biomedical and clinical sciences | |
dc.subject.fieldofresearchcode | 31 | |
dc.subject.fieldofresearchcode | 310199 | |
dc.subject.fieldofresearchcode | 32 | |
dc.title | In-depth N-glycome profiling of paired colorectal cancer and non-tumorigenic tissues reveals cancer-, stage- and EGFR-specific protein N-glycosylation | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Packer, Nicki | |