0 263

Cited 36 times in

In-depth N-glycome profiling of paired colorectal cancer and non-tumorigenic tissues reveals cancer-, stage- and EGFR-specific protein N-glycosylation

 Manveen K Sethi  ;  Hoguen Kim  ;  Cheol Keun Park  ;  Mark S Baker  ;  Young-Ki Paik  ;  Nicolle H Packer  ;  William S Hancock  ;  Susan Fanayan  ;  Morten Thaysen-Andersen 
 GLYCOBIOLOGY, Vol.25(10) : 1064-1078, 2015 
Journal Title
Issue Date
Adenocarcinoma/metabolism* ; Adult ; Aged ; Carbohydrate Conformation ; Carbohydrate Sequence ; Colorectal Neoplasms/metabolism* ; Glycoproteins/metabolism* ; Glycosylation ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Protein Processing, Post-Translational ; Proteome/metabolism ; Receptor, Epidermal Growth Factor/metabolism* ; Sialic Acids/chemistry ; Sialic Acids/metabolism
Colorectal cancer ; EGFR ; N-glycosylation ; glycome ; glycomics
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.
Full Text
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hogeun(김호근)
Park, Cheol Keun(박철근)
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.