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Clin Cancer Res. 2016 Jun 15;22(12):3078-86. doi: 10.1158/1078-0432.CCR-15-1867. Epub 2016 Feb 1.

IgG Glycome in Colorectal Cancer.

Author information

1
Genos Glycoscience Research Laboratory, Zagreb, Croatia.
2
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom. Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Edinburgh, United Kingdom.
3
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Edinburgh, United Kingdom.
4
Faculty of Science, University of Zagreb, Zagreb, Croatia.
5
National Institute for Bioprocessing Research and Training, Dublin, Ireland.
6
Department of Medical Biochemistry and Laboratory Medicine, Clinical Hospital Merkur, Zagreb, Croatia.
7
Allgemein- und Viszeralchirurgie, St. Anna Krankenhaus, Herne, Germany.
8
Department of Health, The National Institute for Health and Welfare, Helsinki, Finland.
9
Polyomica, Groningen, the Netherlands.
10
Genos Glycoscience Research Laboratory, Zagreb, Croatia. Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. glauc@pharma.hr.

Abstract

PURPOSE:

Alternative glycosylation has significant structural and functional consequences on IgG and consequently also on cancer immunosurveillance. Because of technological limitations, the effects of highly heritable individual variations and the differences in the dynamics of changes in IgG glycosylation on colorectal cancer were never investigated before.

EXPERIMENTAL DESIGN:

Using recently developed high-throughput UPLC technology for IgG glycosylation analysis, we analyzed IgG glycome composition in 760 patients with colorectal cancer and 538 matching controls. Effects of surgery were evaluated in 28 patients sampled before and three times after surgery. A predictive model was built using regularized logistic regression and evaluated using a 10-cross validation procedure. Furthermore, IgG glycome composition was analyzed in 39 plasma samples collected before initial diagnosis of colorectal cancer.

RESULTS:

We have found that colorectal cancer associates with decrease in IgG galactosylation, IgG sialylation and increase in core-fucosylation of neutral glycans with concurrent decrease of core-fucosylation of sialylated glycans. Although a model based on age and sex did not show discriminative power (AUC = 0.499), the addition of glycan variables into the model considerably increased the discriminative power of the model (AUC = 0.755). However, none of these differences were significant in the small set of samples collected before the initial diagnosis.

CONCLUSIONS:

Considering the functional relevance of IgG glycosylation for both tumor immunosurveillance and clinical efficacy of therapy with mAbs, individual variation in IgG glycosylation may turn out to be important for prediction of disease course or the choice of therapy, thus warranting further, more detailed studies of IgG glycosylation in colorectal cancer. Clin Cancer Res; 22(12); 3078-86. ©2016 AACR.

PMID:
26831718
PMCID:
PMC5860729
DOI:
10.1158/1078-0432.CCR-15-1867
[Indexed for MEDLINE]
Free PMC Article

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