Alpha-1-acid glycoprotein 1 (AGP1) as a novel biomarker for pancreatic cancer.

Abstract

e15708 Background: Pancreatic cancer is a heterogeneous disease with an aggressive clinical course. Most patients are detected late due to the insidious onset of symptoms and lack of effective molecular markers. The purpose of this study was to develop protein markers for improved prognostication and non-invasive diagnosis. Methods: 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 panel of 80 serum samples with ELISA. Results: Protein sequencing with nano-liquid chromatography tandem MS (nano-LC-MS/MS) and targeted PRM identified alpha-1-acid glycoprotein 1 (AGP1) as a potential pancreatic cancer biomarker. Using TMA and immunohistochemistry, AGP1 expression was significantly associated with shorter overall survival (HR = 2.217; 95% CI 1.296-3.794, p = 0.004). Multivariable analysis confirmed the results (HR = 1.867; 95% CI 1.078-3.235, p = 0.026). Circulating levels of AGP1 yielded an area under the curve (AUC) of 0.85 for the discrimination of resectable pancreatic cancer and IPMN from healthy controls. Combining AGP1 with CA 19-9 displayed an AUC of 0.98 with an overall sensitivity of 96% at 90% specificity. Conclusions: This study suggests that AGP1 is a valid biomarker for pancreatic cancer.