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 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.
The Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK.|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.
Evropi
E
Theodoratou
Genos Glycoscience Research Laboratory, Zagreb, Croatia, HR-10000.
Kujtim
K
Thaçi
Pharmatics Limited, Edinburgh Bioquarter, 9 Little France Road, Edinburgh, EH16 4UX, UK.
Felix
F
Agakov
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.
Maria N
MN
Timofeeva
Genos Glycoscience Research Laboratory, Zagreb, Croatia, HR-10000.
Jerko
J
Štambuk
Genos Glycoscience Research Laboratory, Zagreb, Croatia, HR-10000.
Maja
M
Pučić-Baković
Genos Glycoscience Research Laboratory, Zagreb, Croatia, HR-10000.
Frano
F
Vučković
Pharmatics Limited, Edinburgh Bioquarter, 9 Little France Road, Edinburgh, EH16 4UX, UK.
Peter
P
Orchard
Pharmatics Limited, Edinburgh Bioquarter, 9 Little France Road, Edinburgh, EH16 4UX, UK.
Anna
A
Agakova
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.
Farhat V N
FV
Din
The Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XR, UK.
Ewan
E
Brown
National Institute for Bioprocessing Research &Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland.
Pauline M
PM
Rudd
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.
Susan M
SM
Farrington
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.
Malcolm G
MG
Dunlop
The Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK.|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.
Harry
H
Campbell
Genos Glycoscience Research Laboratory, Zagreb, Croatia, HR-10000.|University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia, HR-10000.
Gordan
G
Lauc
D000368:Aged; D000465:Algorithms; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D006023:Glycoproteins
D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; C046179:glycosylated IgG; D006023:Glycoproteins