Cargando…

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

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 po...

Descripción completa

Detalles Bibliográficos
Autores principales: Krishnan, Shibu, Whitwell, Harry J., Cuenco, Joy, Gentry-Maharaj, Aleksandra, Menon, Usha, Pereira, Stephen P., Gaspari, Marco, Timms, John F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751272/
https://www.ncbi.nlm.nih.gov/pubmed/29232830
http://dx.doi.org/10.3390/ijms18122670
_version_ 1783289913043582976
author Krishnan, Shibu
Whitwell, Harry J.
Cuenco, Joy
Gentry-Maharaj, Aleksandra
Menon, Usha
Pereira, Stephen P.
Gaspari, Marco
Timms, John F.
author_facet Krishnan, Shibu
Whitwell, Harry J.
Cuenco, Joy
Gentry-Maharaj, Aleksandra
Menon, Usha
Pereira, Stephen P.
Gaspari, Marco
Timms, John F.
author_sort Krishnan, Shibu
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5751272
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-57512722018-01-08 Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis Krishnan, Shibu Whitwell, Harry J. Cuenco, Joy Gentry-Maharaj, Aleksandra Menon, Usha Pereira, Stephen P. Gaspari, Marco Timms, John F. Int J Mol Sci Article 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. MDPI 2017-12-09 /pmc/articles/PMC5751272/ /pubmed/29232830 http://dx.doi.org/10.3390/ijms18122670 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krishnan, Shibu
Whitwell, Harry J.
Cuenco, Joy
Gentry-Maharaj, Aleksandra
Menon, Usha
Pereira, Stephen P.
Gaspari, Marco
Timms, John F.
Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis
title Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis
title_full Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis
title_fullStr Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis
title_full_unstemmed Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis
title_short Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis
title_sort evidence of altered glycosylation of serum proteins prior to pancreatic cancer diagnosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751272/
https://www.ncbi.nlm.nih.gov/pubmed/29232830
http://dx.doi.org/10.3390/ijms18122670
work_keys_str_mv AT krishnanshibu evidenceofalteredglycosylationofserumproteinspriortopancreaticcancerdiagnosis
AT whitwellharryj evidenceofalteredglycosylationofserumproteinspriortopancreaticcancerdiagnosis
AT cuencojoy evidenceofalteredglycosylationofserumproteinspriortopancreaticcancerdiagnosis
AT gentrymaharajaleksandra evidenceofalteredglycosylationofserumproteinspriortopancreaticcancerdiagnosis
AT menonusha evidenceofalteredglycosylationofserumproteinspriortopancreaticcancerdiagnosis
AT pereirastephenp evidenceofalteredglycosylationofserumproteinspriortopancreaticcancerdiagnosis
AT gasparimarco evidenceofalteredglycosylationofserumproteinspriortopancreaticcancerdiagnosis
AT timmsjohnf evidenceofalteredglycosylationofserumproteinspriortopancreaticcancerdiagnosis