Serum fucosylated receptor expression-enhancing protein 5 as a biomarker for early stage pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is a leading cause of cancer mortality. Early diagnosis is difficult due to the anatomical characteristics of the pancreas, which is a long and thin organ located dorsal to the stomach and large intestine. The aim of the present study was to search for protein biomarkers for PDAC in serum extracellular vesicles (EVs) using mass spectrometry, and to validate identified biomarkers using an enzyme-linked immunosorbent assay (ELISA) of sera from patients. Comprehensive and targeted proteomic analyses for biomarker discovery and verification were performed using EVs from serum of patients with PDAC, patients with chronic pancreatitis (PT) and healthy volunteers (HVs). For validation, the discriminatory power of candidate proteins was evaluated using an ELISA. Of the 3,043 proteins analyzed, 45 were identified as potential biomarkers, with receptor expression-enhancing protein 5 (REEP5) selected for further analysis. The serum level of fucosylated REEP5 was significantly higher in PDAC cases compared with in PT and HVs (P<0.001). The areas under the curve (AUC) of the receiver operator characteristic were 0.928 for fucosylated REEP5 and 0.805 for carbohydrate antigen 19-9 (CA19-9) in PDAC vs. non-cancer controls. The AUCs were 0.962 for fucosylated REEP5 and 0.810 for CA19-9 in stages I and II of PDAC. These results indicate that fucosylated REEP5 is a novel serum EV biomarker for detection of early stage PDAC. Further analysis in a larger cohort is warranted to evaluate the clinical utility of fucosylated REEP5 as a biomarker for PDAC.