TY - JOUR
T1 - Expression of the Antiapoptotic Protein BAG3 Is a Feature of Pancreatic Adenocarcinoma and Its Overexpression Is Associated With Poorer Survival
AU - Rosati, Alessandra
AU - Bersani, Samantha
AU - Tavano, Francesca
AU - Dalla Pozza, Elisa
AU - de Marco, Margot
AU - Palmieri, Marta
AU - de Laurenzi, Vincenzo
AU - Franco, Renato
AU - Scognamiglio, Giosuè
AU - Palaia, Raffaele
AU - Fontana, Andrea
AU - di Sebastiano, Pierluigi
AU - Donadelli, Massimo
AU - Dando, Ilaria
AU - Medema, Jan Paul
AU - Dijk, Frederike
AU - Welling, Lieke
AU - di Mola, Fabio Francesco
AU - Pezzilli, Raffaele
AU - Turco, Maria Caterina
AU - Scarpa, Aldo
PY - 2012
Y1 - 2012
N2 - 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. (Am J Pathol 2012, 181: 1524-1529; http://dx.doi.org/10.1016/j.ajpath.2012.07.016)
AB - 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. (Am J Pathol 2012, 181: 1524-1529; http://dx.doi.org/10.1016/j.ajpath.2012.07.016)
U2 - https://doi.org/10.1016/j.ajpath.2012.07.016
DO - https://doi.org/10.1016/j.ajpath.2012.07.016
M3 - Article
C2 - 22944597
SN - 0002-9440
VL - 181
SP - 1524
EP - 1529
JO - American journal of pathology
JF - American journal of pathology
IS - 5
ER -