title: IgG Glycome in Colorectal Cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Frano
authors.initials: F
authors.lastname: Vučković
authors.affiliation: 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.
authors.forename: Evropi
authors.initials: E
authors.lastname: Theodoratou
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Kujtim
authors.initials: K
authors.lastname: Thaçi
authors.affiliation: Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Edinburgh, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Timofeeva
authors.affiliation: Faculty of Science, University of Zagreb, Zagreb, Croatia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Vojta
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Jerko
authors.initials: J
authors.lastname: Štambuk
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Pučić-Baković
authors.affiliation: National Institute for Bioprocessing Research and Training, Dublin, Ireland.
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.affiliation: Department of Medical Biochemistry and Laboratory Medicine, Clinical Hospital Merkur, Zagreb, Croatia.
authors.forename: Lovorka
authors.initials: L
authors.lastname: Đerek
authors.affiliation: Allgemein- und Viszeralchirurgie, St. Anna Krankenhaus, Herne, Germany.
authors.forename: Dražen
authors.initials: D
authors.lastname: Servis
authors.affiliation: Department of Health, The National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Annika
authors.initials: A
authors.lastname: Wennerström
authors.affiliation: Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Edinburgh, United Kingdom.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Farrington
authors.affiliation: Department of Health, The National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: Polyomica, Groningen, the Netherlands.
authors.forename: Yurii
authors.initials: Y
authors.lastname: Aulchenko
authors.affiliation: Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Edinburgh, United Kingdom.
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Dunlop
authors.affiliation: 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.
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia. Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. glauc@pharma.hr.
authors.forename: Gordan
authors.initials: G
authors.lastname: Lauc
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000276:immunology* / Q000601:surgery; D005247:Feeding Behavior; D005260:Female; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011499:Protein Processing, Post-Translational / Q000276:immunology; D011795:Surveys and Questionnaires; D006023:Glycoproteins
chemical_list: D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; C046179:glycosylated IgG; D006023:Glycoproteins
references.citation: Clin Cancer Res. 2013 Mar 1;19(5):1126-38
references.pmid: 23209031
references.citation: Dis Markers. 2008;25(4-5):267-78
references.pmid: 19126970
references.citation: Blood. 2002 Feb 1;99(3):754-8
references.pmid: 11806974
references.citation: Blood. 2014 Jan 23;123(4):471-80
references.pmid: 24243971
references.citation: Clin Cancer Res. 2011 Apr 15;17(8):2444-50
references.pmid: 21270110
references.citation: Arthritis Rheumatol. 2015 Nov;67(11):2978-89
references.pmid: 26200652
references.citation: Immunol Lett. 2014 Aug;160(2):139-44
references.pmid: 24495619
references.citation: Br Med J. 1957 Apr 6;1(5022):779-86
references.pmid: 13404306
references.citation: Clin Cancer Res. 2006 May 1;12(9):2879-87
references.pmid: 16675584
references.citation: Mol Cell Proteomics. 2011 Oct;10(10):M111.010090
references.pmid: 21653738
references.citation: Nat Rev Immunol. 2013 Mar;13(3):176-89
references.pmid: 23411799
references.citation: Inflamm Bowel Dis. 2015 Jun;21(6):1237-47
references.pmid: 25895110
references.citation: PLoS One. 2014 Apr 14;9(4):e94536
references.pmid: 24732908
references.citation: Annu Rev Immunol. 2011;29:235-71
references.pmid: 21219185
references.citation: J Clin Immunol. 2014 Jul;34 Suppl 1:S51-5
references.pmid: 24760108
references.citation: J Gerontol A Biol Sci Med Sci. 2014 Jul;69(7):779-89
references.pmid: 24325898
references.citation: Br J Cancer. 2014 Mar 4;110(5):1221-7
references.pmid: 24496456
references.citation: Mol Cancer Res. 2007 Dec;5(12):1263-75
references.pmid: 18171984
references.citation: J Biol Chem. 2003 Jan 31;278(5):3466-73
references.pmid: 12427744
references.citation: Int J Cancer. 2012 Apr 1;130(7):1558-66
references.pmid: 21544814
references.citation: Arthritis Rheum. 2010 Aug;62(8):2239-48
references.pmid: 20506563
references.citation: PLoS One. 2013 Dec 06;8(12):e82558
references.pmid: 24324808
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):630-5
references.pmid: 23267084
references.citation: Ann Rheum Dis. 2015 Jan;74(1):234-41
references.pmid: 24106048
references.citation: Biochim Biophys Acta. 2012 Sep;1820(9):1318-26
references.pmid: 22183029
references.citation: J Biol Chem. 2006 Feb 24;281(8):5032-6
references.pmid: 16330541
references.citation: Sci Rep. 2014 Mar 11;4:4347
references.pmid: 24614541
references.citation: PLoS Genet. 2013;9(1):e1003225
references.pmid: 23382691
references.citation: Nucleic Acids Res. 2002 Jan 1;30(1):207-10
references.pmid: 11752295
references.citation: Mol Immunol. 2006 Mar;43(8):1183-93
references.pmid: 16102830
references.citation: Nat Rev Immunol. 2010 May;10(5):317-27
references.pmid: 20414205
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):684-93
references.pmid: 17416758
references.citation: Adv Immunol. 2014;124:67-94
references.pmid: 25175773
references.citation: Cancer Immun. 2012;12:13
references.pmid: 22896758
references.citation: Nature. 1985 Aug 1-7;316(6027):452-7
references.pmid: 3927174
references.citation: Int J Epidemiol. 2010 Apr;39(2):504-18
references.pmid: 19959603
references.citation: Gut. 1990 Apr;31(4):431-4
references.pmid: 2338269
references.citation: Sci Rep. 2014 Sep 01;4:6145
references.pmid: 25174450
references.citation: Glycobiology. 2014 Oct;24(10):935-44
references.pmid: 24906821
references.citation: J Clin Oncol. 2007 Aug 20;25(24):3712-8
references.pmid: 17704420
references.citation: Chem Biol. 2014 Jan 16;21(1):16-37
references.pmid: 24269151
references.citation: Nat Chem Biol. 2013 Dec;9(12):776-84
references.pmid: 24231619
references.citation: Nat Rev Immunol. 2008 Jan;8(1):34-47
references.pmid: 18064051