Proteomic analysis of pancreatic juice for the identification of biomarkers of pancreatic cancer

Abstract

Protein profiles of endoscopically collected pancreatic juice from normal, chronic pancreatitis patients and pancreatic cancer patients were compared to identify diagnostic biomarkers of pancreatic cancer. Secretin was injected intravenously and pancreatic juice was collected via selective cannulation of the pancreatic duct during endoscopic retrograde cholangiopancreatography. Pancreatic juices consisting of three pooled samples for normal control, chronic pancreatitis, and pancreatic cancer patients were compared using two-dimensional gel electrophoresis, and the proteins were subsequently identified using MALDI-TOF-MS. Thirty-five protein spots were up-regulated twofold in pancreatic cancer compared with the levels in the normal controls, and 85 protein spots were present in pancreatic cancer samples but not in normal controls. After excluding spots that were also expressed in chronic pancreatitis, 26 protein spots that were up-regulated or only expressed in pancreatic cancer samples were identified. Among the identified proteins, we confirmed the expressions of BIG2, PRDX6, and REG1α in pancreatic cancer tissue using immunohistochemistry. ELISA showed that the serum level of REG1α was significantly higher in patients with pancreatic cancer than it was in the normal controls (P=0.023). With the best cut-off value, the sensitivity and specificity of REG1α to differentiate normal and pancreatic cancer were 82.6 and 81.8%, compared with 69.6 and 100% for CA19-9. We have shown that pancreatic juice is a good source of pancreatic cancer tumor markers. Further studies are needed to determine the clinical implications of REG1α and other markers.