Abstract
Objectives: Chronic pancreatitis (CP) is a high-risk factor for pancreatic ductal adenocarcinoma (PDAC).
However, as most CP patients have few symptoms, serum biomarkers for subclinical CP would be of great clinical
benefit. Previously, we identified the fucosylated Mac-2 binding protein (Mac-2bp) as a novel CP biomarker.
Fucosylation is one of the most important glycosylations involved in cancer and inflammatory diseases,
because fucosylated proteins are often secreted with the loss of cell polarization. Here, focusing on fucosylated
pancreatic glycoproteins, we used glycoproteomics to identify a novel CP biomarker. Methods: Fucosylated
proteins in pancreatic juices from PDAC patients were identified by Aleuria aurantia lectin (AAL) affinity
chromatography followed by mass spectrometry. Levels of serum S100A8, which would bind to fucosylated
proteins, were measured by an enzyme-linked immunosorbent assay in 135 healthy volunteers (HV) and
159 clinically diagnosed CP patients. Results: Approximately 30 fucosylated proteins in pancreatic juice were
identified. We focused on S100A8, which was enriched by AAL chromatography. Serum S100A8 levels were
significantly higher in CP patients than in HV controls. The area under the receiver operating characteristic
(AUROC) curve for S100A8 and Mac-2bp, which we previously identified as glyco-biomarkers that distinguish CP patients from HV controls, was 0.803 and 0.690, respectively. The combination of S100A8 and Mac-2bp
gave an AUROC of 0.827, which improved the diagnostic ability for CP. Conclusion: A combination of two fucosylation-
related proteins, S100A8 and Mac-2bp, may serve as a candidate biomarker for CP diagnosis.
