TY - JOUR
T1 - Alpha-1-acid glycoprotein 1 is upregulated in pancreatic ductal adenocarcinoma and confers a poor prognosis
AU - Zhou, Qimin
AU - Andersson, Roland
AU - Hu, Dingyuan
AU - Bauden, Monika
AU - Sasor, Agata
AU - Bygott, Thomas
AU - PawŁowski, Krzysztof
AU - Pla, Indira
AU - Marko-Varga, György
AU - Ansari, Daniel
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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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U2 - 10.1016/j.trsl.2019.06.003
DO - 10.1016/j.trsl.2019.06.003
M3 - Article
C2 - 31295437
AN - SCOPUS:85068769496
SN - 1931-5244
VL - 212
SP - 67
EP - 79
JO - Translational Research
JF - Translational Research
ER -