DLL4 expression is a prognostic marker and may predict gemcitabine benefit in resected pancreatic cancer

{Background: There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4) as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC). Methods: Using immunohistochemistry (IHC) and tissue microarray (TMA), we assessed the expression patterns of DLL4, Notch1 and Notch3 in 151 patients from two independent cohorts of resected PDAC. We investigated the prognostic and the predictive significance of these proteins. Results: High IHC DLL4 expression in cancer cells was associated with worse overall survival (OS) and disease-free survival (DFS) than low DLL4 expression (median OS: 12.9 vs 30.4 months, P - 0.004 and median DFS: 8.8 vs 17.4 months, P - 0.02). High DLL4 expression remained a significant negative prognostic factor in multivariate analysis (HR for OS: 2.1