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Sci Rep. 2016 Jun 15;6:28098. doi: 10.1038/srep28098.

Glycosylation of plasma IgG in colorectal cancer prognosis.

Author information

1
The Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK.
2
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Crewe Road, Edinburgh, EH4 2XU, UK.
3
Genos Glycoscience Research Laboratory, Zagreb, Croatia, HR-10000.
4
Pharmatics Limited, Edinburgh Bioquarter, 9 Little France Road, Edinburgh, EH16 4UX, UK.
5
The Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XR, UK.
6
National Institute for Bioprocessing Research &Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland.
7
University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia, HR-10000.

Abstract

In this study we demonstrate the potential value of Immunoglobulin G (IgG) glycosylation as a novel prognostic biomarker of colorectal cancer (CRC). We analysed plasma IgG glycans in 1229 CRC patients and correlated with survival outcomes. We assessed the predictive value of clinical algorithms and compared this to algorithms that also included glycan predictors. Decreased galactosylation, decreased sialylation (of fucosylated IgG glycan structures) and increased bisecting GlcNAc in IgG glycan structures were strongly associated with all-cause (q < 0.01) and CRC mortality (q = 0.04 for galactosylation and sialylation). Clinical algorithms showed good prediction of all-cause and CRC mortality (Harrell's C: 0.73, 0.77; AUC: 0.75, 0.79, IDI: 0.02, 0.04 respectively). The inclusion of IgG glycan data did not lead to any statistically significant improvements overall, but it improved the prediction over clinical models for stage 4 patients with the shortest follow-up time until death, with the median gain in the test AUC of 0.08. These glycan differences are consistent with significantly increased IgG pro-inflammatory activity being associated with poorer CRC prognosis, especially in late stage CRC. In the absence of validated biomarkers to improve upon prognostic information from existing clinicopathological factors, the potential of these novel IgG glycan biomarkers merits further investigation.

PMID:
27302279
PMCID:
PMC4908421
DOI:
10.1038/srep28098
[Indexed for MEDLINE]
Free PMC Article

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