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

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Title: Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis
Authors: Krishnan, S
Whitwell, HJ
Cuenco, J
Gentry-Maharaj, A
Menon, U
Pereira, SP
Gaspari, M
Timms, JF
Item Type: Journal Article
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.
Issue Date: 9-Dec-2017
Date of Acceptance: 6-Dec-2017
URI: http://hdl.handle.net/10044/1/57159
DOI: https://dx.doi.org/10.3390/ijms18122670
ISSN: 1422-0067
Publisher: MDPI AG
Journal / Book Title: International Journal of Molecular Sciences
Volume: 18
Issue: 12
Copyright Statement: 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).
Keywords: Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
Chemistry
pancreatic cancer
biomarkers
N-glycosylation
serum
titanium dioxide
UKCTOCS
ACUTE-PHASE PROTEINS
MASS-SPECTROMETRY
DUCTAL ADENOCARCINOMA
CARCINOEMBRYONIC ANTIGEN
ASYMPTOMATIC POPULATION
DIGESTIVE-SYSTEM
CLINICAL UTILITY
OVARIAN-CANCER
CA-19-9
CA19-9
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Chemical Physics
Publication Status: Published
Article Number: 2670
Appears in Collections:Faculty of Engineering
Chemical Engineering



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