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Alpha-1-acid glycoprotein 1 is upregulated in pancreatic ductal adenocarcinoma and confers a poor prognosis

Zhou, Q. LU orcid ; Andersson, Roland LU ; Hu, Dingyuan LU ; Bauden, Monika LU orcid ; Sasor, A. LU ; Bygott, Thomas ; PawŁowski, Krzysztof LU ; Pla, Indira LU orcid ; Marko-Varga, György LU and Ansari, Daniel LU (2019) In Translational Research 212. p.67-79
Abstract

Pancreatic cancer is an aggressive malignancy that carries a high mortality rate. A major contributor to the poor outcome is the lack of effective molecular markers. The purpose of this study was to develop protein markers for improved prognostication and noninvasive diagnosis. A mass spectrometry (MS)-based discovery approach was applied to pancreatic cancer tissues and healthy pancreas. In the verification phase, extracellular proteins with differential expression were further quantified in targeted mode using parallel reaction monitoring (PRM). Next, a tissue microarray (TMA) cohort including 140 pancreatic cancer resection specimens was constructed, in order to validate protein expression status and investigate potential prognostic... (More)

Pancreatic cancer is an aggressive malignancy that carries a high mortality rate. A major contributor to the poor outcome is the lack of effective molecular markers. The purpose of this study was to develop protein markers for improved prognostication and noninvasive diagnosis. A mass spectrometry (MS)-based discovery approach was applied to pancreatic cancer tissues and healthy pancreas. In the verification phase, extracellular proteins with differential expression were further quantified in targeted mode using parallel reaction monitoring (PRM). Next, a tissue microarray (TMA) cohort including 140 pancreatic cancer resection specimens was constructed, in order to validate protein expression status and investigate potential prognostic implications. The levels of protein candidates were finally assessed in a prospective series of 110 serum samples in an accredited clinical laboratory using the automated Cobas system. Protein sequencing with nanoliquid chromatography tandem MS (nano-LC-MS/MS) and targeted PRM identified alpha-1-acid glycoprotein 1 (AGP1) as an upregulated protein in pancreatic cancer tissue. Using TMA and immunohistochemistry, AGP1 expression was significantly associated with shorter overall survival (HR = 2.22; 95% CI 1.30–3.79, P = 0.004). Multivariable analysis confirmed the results (HR = 1.87; 95% CI 1.08–3.24, P = 0.026). Circulating levels of AGP1 yielded an area under the curve (AUC) of 0.837 for the discrimination of resectable pancreatic cancer from healthy controls. Combining AGP1 with CA 19-9 enhanced the diagnostic performance, with an AUC of 0.963. This study suggests that AGP1 is a novel prognostic biomarker in pancreatic cancer tissue. Serum AGP1 levels may be useful as part of a biomarker panel for early detection of pancreatic cancer but further studies are needed.

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organization
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type
Contribution to journal
publication status
published
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in
Translational Research
volume
212
pages
13 pages
publisher
Elsevier
external identifiers
  • scopus:85068769496
  • pmid:31295437
ISSN
1931-5244
DOI
10.1016/j.trsl.2019.06.003
language
English
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yes
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f7ad7eaa-c76c-4e71-b9d4-c840b40fa574
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068769496&doi=10.1016%2fj.trsl.2019.06.003&partnerID=40&md5=cbaf7668c5e8ca1a4aa97c9c706ed94f
date added to LUP
2019-07-24 10:55:33
date last changed
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@article{f7ad7eaa-c76c-4e71-b9d4-c840b40fa574,
  abstract     = {{<p>Pancreatic cancer is an aggressive malignancy that carries a high mortality rate. A major contributor to the poor outcome is the lack of effective molecular markers. The purpose of this study was to develop protein markers for improved prognostication and noninvasive diagnosis. A mass spectrometry (MS)-based discovery approach was applied to pancreatic cancer tissues and healthy pancreas. In the verification phase, extracellular proteins with differential expression were further quantified in targeted mode using parallel reaction monitoring (PRM). Next, a tissue microarray (TMA) cohort including 140 pancreatic cancer resection specimens was constructed, in order to validate protein expression status and investigate potential prognostic implications. The levels of protein candidates were finally assessed in a prospective series of 110 serum samples in an accredited clinical laboratory using the automated Cobas system. Protein sequencing with nanoliquid chromatography tandem MS (nano-LC-MS/MS) and targeted PRM identified alpha-1-acid glycoprotein 1 (AGP1) as an upregulated protein in pancreatic cancer tissue. Using TMA and immunohistochemistry, AGP1 expression was significantly associated with shorter overall survival (HR = 2.22; 95% CI 1.30–3.79, P = 0.004). Multivariable analysis confirmed the results (HR = 1.87; 95% CI 1.08–3.24, P = 0.026). Circulating levels of AGP1 yielded an area under the curve (AUC) of 0.837 for the discrimination of resectable pancreatic cancer from healthy controls. Combining AGP1 with CA 19-9 enhanced the diagnostic performance, with an AUC of 0.963. This study suggests that AGP1 is a novel prognostic biomarker in pancreatic cancer tissue. Serum AGP1 levels may be useful as part of a biomarker panel for early detection of pancreatic cancer but further studies are needed.</p>}},
  author       = {{Zhou, Q. and Andersson, Roland and Hu, Dingyuan and Bauden, Monika and Sasor, A. and Bygott, Thomas and PawŁowski, Krzysztof and Pla, Indira and Marko-Varga, György and Ansari, Daniel}},
  issn         = {{1931-5244}},
  language     = {{eng}},
  month        = {{06}},
  pages        = {{67--79}},
  publisher    = {{Elsevier}},
  series       = {{Translational Research}},
  title        = {{Alpha-1-acid glycoprotein 1 is upregulated in pancreatic ductal adenocarcinoma and confers a poor prognosis}},
  url          = {{http://dx.doi.org/10.1016/j.trsl.2019.06.003}},
  doi          = {{10.1016/j.trsl.2019.06.003}},
  volume       = {{212}},
  year         = {{2019}},
}