title: Expression of the antiapoptotic protein BAG3 is a feature of pancreatic adenocarcinoma and its overexpression is associated with poorer survival.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers, being the fourth leading cause of cancer-related deaths. Long-term survival reaching 15% is achieved in less than 5% of patients who undergo surgery, and median survival is only 6 months in those with inoperable lesions. A deeper understanding of PDAC biologic characteristics as well as novel prognostic markers are therefore required to improve outcomes. Herein we report that BAG3, a protein with recognized anti-apoptotic activity, was expressed in 346 PDACs analyzed, but was not expressed in the surrounding nonneoplastic tissue. In a cohort of 66 patients who underwent radical resection (R0), survival was significantly shorter in patients with high BAG3 expression (median, 12 months) than in those with low BAG3 expression (median, 23 months) (P = 0.001). Furthermore, we report that BAG3 expression in PDAC-derived cell lines protects from apoptosis and confers resistance to gemcitabine, offering a partial explanation for the survival data. Our results indicate that BAG3 has a relevant role in PDAC biology, and suggest that BAG3 expression level might be a potential marker for prediction of patient outcome.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Fisciano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rosati
authors.forename: Samantha
authors.initials: S
authors.lastname: Bersani
authors.forename: Francesca
authors.initials: F
authors.lastname: Tavano
authors.forename: Elisa
authors.initials: E
authors.lastname: Dalla Pozza
authors.forename: Margot
authors.initials: M
authors.lastname: De Marco
authors.forename: Marta
authors.initials: M
authors.lastname: Palmieri
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Laurenzi
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Giosuè
authors.initials: G
authors.lastname: Scognamiglio
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palaia
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.forename: Pierluigi
authors.initials: P
authors.lastname: di Sebastiano
authors.forename: Massimo
authors.initials: M
authors.lastname: Donadelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dando
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
authors.forename: Frederike
authors.initials: F
authors.lastname: Dijk
authors.forename: Lieke
authors.initials: L
authors.lastname: Welling
authors.forename: Fabio Francesco
authors.initials: FF
authors.lastname: di Mola
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pezzilli
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Turco
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D016016:Proportional Hazards Models; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine