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High-density and targeted glycoproteomic profiling of serum proteins in pancreatic cancer and intraductal papillary mucinous neoplasm

Aronsson, Linus LU ; Andersson, Roland LU ; Bauden, Monika LU ; Andersson, Bodil LU ; Bygott, Thomas and Ansari, Daniel LU (2018) In Scandinavian Journal of Gastroenterology
Abstract

Objective: Glycoproteomics is an emerging subfield of proteomics. Tumor-specific variations in protein glycosylation might be potential targets for the development of new cancer diagnostics. Here, we performed high-throughput screening and targeted verification of glycome alterations in serum samples from patients with pancreatic cancer and the precancerous lesion intraductal papillary mucinous neoplasm (IPMN). Material and methods: The glycosylation profile of 1000 proteins was mapped in a discovery cohort comprising serum samples from 16 individuals, including 8 patients with pancreatic cancer and 8 healthy controls. The top 10 glycoprotein biomarker candidates with the highest signal intensity difference in glycosylation levels were... (More)

Objective: Glycoproteomics is an emerging subfield of proteomics. Tumor-specific variations in protein glycosylation might be potential targets for the development of new cancer diagnostics. Here, we performed high-throughput screening and targeted verification of glycome alterations in serum samples from patients with pancreatic cancer and the precancerous lesion intraductal papillary mucinous neoplasm (IPMN). Material and methods: The glycosylation profile of 1000 proteins was mapped in a discovery cohort comprising serum samples from 16 individuals, including 8 patients with pancreatic cancer and 8 healthy controls. The top 10 glycoprotein biomarker candidates with the highest signal intensity difference in glycosylation levels were evaluated in a cohort consisting of 109 serum samples, including 49 patients with resectable pancreatic cancer, 13 patients with resectable noninvasive IPMN and 47 healthy controls, using a targeted assay. Results: Multivariable analysis defined sets of panels comprising CA19-9 and distinctively glycosylated proteins for discrimination between pancreatic cancer, IPMN and healthy controls. A panel including CA 19-9, IL.17E, B7.1 and DR6 gave an AUC of 0.988 at 100% sensitivity at 90% specificity for the discrimination of stage 1 pancreatic cancer and healthy controls. B7.1 was found to be a valuable biomarker for differentiating between IPMN and healthy controls, with better performance alone than CA 19-9. Conclusions: Measurement of protein glycosylation profiles in serum may aid in the early detection of pancreatic cancer and precursor lesions.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
biomarker, early diagnosis, Glycoproteomics, intraductal papillary mucinous neoplasm, pancreatic cancer, serum
in
Scandinavian Journal of Gastroenterology
publisher
Taylor & Francis
external identifiers
  • scopus:85058126681
ISSN
0036-5521
DOI
10.1080/00365521.2018.1532020
language
English
LU publication?
yes
id
5114864b-b116-4286-a0c4-d7d2d68c8fdc
date added to LUP
2019-01-02 09:53:05
date last changed
2019-02-20 11:40:59
@article{5114864b-b116-4286-a0c4-d7d2d68c8fdc,
  abstract     = {<p>Objective: Glycoproteomics is an emerging subfield of proteomics. Tumor-specific variations in protein glycosylation might be potential targets for the development of new cancer diagnostics. Here, we performed high-throughput screening and targeted verification of glycome alterations in serum samples from patients with pancreatic cancer and the precancerous lesion intraductal papillary mucinous neoplasm (IPMN). Material and methods: The glycosylation profile of 1000 proteins was mapped in a discovery cohort comprising serum samples from 16 individuals, including 8 patients with pancreatic cancer and 8 healthy controls. The top 10 glycoprotein biomarker candidates with the highest signal intensity difference in glycosylation levels were evaluated in a cohort consisting of 109 serum samples, including 49 patients with resectable pancreatic cancer, 13 patients with resectable noninvasive IPMN and 47 healthy controls, using a targeted assay. Results: Multivariable analysis defined sets of panels comprising CA19-9 and distinctively glycosylated proteins for discrimination between pancreatic cancer, IPMN and healthy controls. A panel including CA 19-9, IL.17E, B7.1 and DR6 gave an AUC of 0.988 at 100% sensitivity at 90% specificity for the discrimination of stage 1 pancreatic cancer and healthy controls. B7.1 was found to be a valuable biomarker for differentiating between IPMN and healthy controls, with better performance alone than CA 19-9. Conclusions: Measurement of protein glycosylation profiles in serum may aid in the early detection of pancreatic cancer and precursor lesions.</p>},
  author       = {Aronsson, Linus and Andersson, Roland and Bauden, Monika and Andersson, Bodil and Bygott, Thomas and Ansari, Daniel},
  issn         = {0036-5521},
  keyword      = {biomarker,early diagnosis,Glycoproteomics,intraductal papillary mucinous neoplasm,pancreatic cancer,serum},
  language     = {eng},
  month        = {12},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Gastroenterology},
  title        = {High-density and targeted glycoproteomic profiling of serum proteins in pancreatic cancer and intraductal papillary mucinous neoplasm},
  url          = {http://dx.doi.org/10.1080/00365521.2018.1532020},
  year         = {2018},
}