An integrated cross-species approach for the discovery of serum-based diagnostic biomarkers of PDAC using a genetically engineered murine model (GEMM).

218 Background: The development of sensitive and specific biomarkers for the early diagnosis of human pancreatic ductal adenocarcinoma (PDAC) represents a major unmet clinical need. GEMMs that faithfully recapitulate the clinical, histological and molecular features of PDAC and capture its genomic complexity (including that triggered by a truncating germline Brca2 mutation) coupled with state of the art proteomic technologies can overcome some of the challenges associated with the analysis of a heterogeneous human disease. We have conducted a large scale screen for differentially expressed glycoproteins in pancreatic tissue and serum from mice with PDAC, pancreatic intra-epithelial neoplasia (PanIN) and matched healthy controls, using the well validated KPCB model of PDAC. Methods: Tryptic digests of protein extracts from snap frozen PDAC, pre-malignant and normal pancreata were subjected to solid-phase extraction of N-glycopeptides and the samples were analysed on a LTQ Orbitrap XL mass spectrometer. LC-...