Expression of the antiapoptotic protein BAG3 is a feature of pancreatic adenocarcinoma and its overexpression is associated with poorer survival

Pancreatic ductal adenocarcinoma (PDAC) is one ofthe most deadly cancers, being the fourth leadingcause of cancer-related deaths. Long-term survivalreaching 15% is achieved in less than 5% of patientswho undergo surgery, and median survival is only 6months in those with inoperable lesions. A deeperunderstanding of PDAC biologic characteristics aswell as novel prognostic markers are therefore requiredto improve outcomes. Herein we report that BAG3, a protein with recognized anti-apoptotic activity,was expressed in 346 PDACs analyzed, but was notexpressed in the surrounding nonneoplastic tissue.In a cohort of 66 patients who underwent radicalresection (R0), survival was significantly shorter inpatients with high BAG3 expression (median, 12months) than in those with low BAG3 expression(median, 23 months) (P 0.001). Furthermore, wereport that BAG3 expression in PDAC-derived celllines protects from apoptosis and confers resistanceto gemcitabine, offering a partial explanation for thesurvival data. Our results indicate that BAG3 has arelevant role in PDAC biology, and suggest that BAG3expression level might be a potential marker for predictionof patient outcome.