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Int. J. Mol. Sci. 2017, 18(12), 2670; https://doi.org/10.3390/ijms18122670

Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis

1
Research Center for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University of Catanzaro ‘Magna Graecia’, 88100 Catanzaro, Italy
2
Institute for Women’s Health, University College London, Gower Street, London WC1E 6BT, UK
3
Institute for Liver and Digestive Health, Royal Free Hospital Campus, University College London, London NW3 2QG, UK
*
Author to whom correspondence should be addressed.
Received: 13 November 2017 / Revised: 5 December 2017 / Accepted: 6 December 2017 / Published: 9 December 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Biomarkers for the early detection of pancreatic cancer are urgently needed. The aim of this pilot study was to evaluate changes in serum N-glycoproteins and their glycosylation status prior to clinical presentation of pancreatic cancer that may be potential biomarkers. Prediagnosis serum samples pooled according to five time-to-diagnosis groups and a non-cancer control pool were digested with trypsin, labelled with mass tags, and subjected to titanium dioxide capture, deglycosylation, and 2D-LC-MS/MS profiling. Unbound peptides were profiled in parallel. Across the sample groups, 703 proteins were quantified and 426 putative sites of N-glycosylation were identified with evidence of several novel sites. Altered proteins with biomarker potential were predominantly abundant inflammatory response, coagulation, and immune-related proteins. Whilst glycopeptide profiles largely paralleled those of their parent proteins, there was evidence of altered N-glycosylation site occupancy or sialic acid content prior to diagnosis for some proteins, most notably of immunoglobulin gamma chains. α-1-Antitrypsin was tested as a biomarker, but found not to complement carbohydrate antigen 19-9 (CA19-9) in early detection of cancer. In conclusion, we provide preliminary evidence of altered glycosylation of several serum proteins prior to pancreatic cancer diagnosis, warranting further investigation of these proteins as early biomarkers. These changes may be largely driven by inflammatory processes that occur in response to tumour formation and progression. View Full-Text
Keywords: pancreatic cancer; biomarkers; N-glycosylation; serum; titanium dioxide; UKCTOCS pancreatic cancer; biomarkers; N-glycosylation; serum; titanium dioxide; UKCTOCS
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Krishnan, S.; Whitwell, H.J.; Cuenco, J.; Gentry-Maharaj, A.; Menon, U.; Pereira, S.P.; Gaspari, M.; Timms, J.F. Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis. Int. J. Mol. Sci. 2017, 18, 2670.

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