Pancreatic ductal adenocarcinomas (PDAC) form the largest subset of pancreatic cancers and are considered one of the most lethal diseases with a global overall 5-year survival rate of 9 %. For the differential diagnosis of benign neoplasia, chronic pancreatitis or carcinomas, often an invasive, histopathologic examination needs to be performed. Consequently, the development of a non-invasive liquid biopsy-based method for the differential diagnosis of pancreatic diseases would represent a significant clinical advance.

The objective of this study was to identify differentially expressed serum proteins by comparing protein profiles between healthy controls and patients with pancreatic diseases (n=73, e.g. PDAC, IPMN, …) using LC-MS/MS (liquid chromatography-mass spectrometry/mass spectrometry) in data-independent acquisition mode (SWATH).

280 serum proteins were identified, quantified and revealed distinct separations between PDAC and benign pancreatic lesions such as pseudocysts, cystadenomas, and IPMNs (intraductal papillary mucinous neoplasia) using clustering analyses. Statistical evaluation revealed eight significant protein expression differences between the healthy, benign, and malignant group (FC > 1.5 & q-value < 0.05). Analysis through Panther pathway analysis showed that significant protein expressions of the malignant group were associated with processes like the coagulation cascade or inflammatory processes.

This study demonstrates significant differences in the global serum protein expression between patients with malignant and benign pancreatic diseases. Protein targets were identified by quantitative mass spectrometry and will be further validated for their potential as biomarkers.