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Glycosylation of plasma IgG in colorectal cancer prognosis
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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908421/ https://www.ncbi.nlm.nih.gov/pubmed/27302279 http://dx.doi.org/10.1038/srep28098 |
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author | Theodoratou, Evropi Thaçi, Kujtim Agakov, Felix Timofeeva, Maria N. Štambuk, Jerko Pučić-Baković, Maja Vučković, Frano Orchard, Peter Agakova, Anna Din, Farhat V. N. Brown, Ewan Rudd, Pauline M. Farrington, Susan M. Dunlop, Malcolm G. Campbell, Harry Lauc, Gordan |
author_facet | Theodoratou, Evropi Thaçi, Kujtim Agakov, Felix Timofeeva, Maria N. Štambuk, Jerko Pučić-Baković, Maja Vučković, Frano Orchard, Peter Agakova, Anna Din, Farhat V. N. Brown, Ewan Rudd, Pauline M. Farrington, Susan M. Dunlop, Malcolm G. Campbell, Harry Lauc, Gordan |
author_sort | Theodoratou, Evropi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4908421 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49084212016-06-15 Glycosylation of plasma IgG in colorectal cancer prognosis Theodoratou, Evropi Thaçi, Kujtim Agakov, Felix Timofeeva, Maria N. Štambuk, Jerko Pučić-Baković, Maja Vučković, Frano Orchard, Peter Agakova, Anna Din, Farhat V. N. Brown, Ewan Rudd, Pauline M. Farrington, Susan M. Dunlop, Malcolm G. Campbell, Harry Lauc, Gordan Sci Rep Article 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. Nature Publishing Group 2016-06-15 /pmc/articles/PMC4908421/ /pubmed/27302279 http://dx.doi.org/10.1038/srep28098 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Theodoratou, Evropi Thaçi, Kujtim Agakov, Felix Timofeeva, Maria N. Štambuk, Jerko Pučić-Baković, Maja Vučković, Frano Orchard, Peter Agakova, Anna Din, Farhat V. N. Brown, Ewan Rudd, Pauline M. Farrington, Susan M. Dunlop, Malcolm G. Campbell, Harry Lauc, Gordan Glycosylation of plasma IgG in colorectal cancer prognosis |
title | Glycosylation of plasma IgG in colorectal cancer prognosis |
title_full | Glycosylation of plasma IgG in colorectal cancer prognosis |
title_fullStr | Glycosylation of plasma IgG in colorectal cancer prognosis |
title_full_unstemmed | Glycosylation of plasma IgG in colorectal cancer prognosis |
title_short | Glycosylation of plasma IgG in colorectal cancer prognosis |
title_sort | glycosylation of plasma igg in colorectal cancer prognosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908421/ https://www.ncbi.nlm.nih.gov/pubmed/27302279 http://dx.doi.org/10.1038/srep28098 |
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