Heat shock protein 27 as a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma

Journal of Cellular and Molecular Medicine

Claus Schäfer⁵  Hendrik Seeliger²  Dominik C. Bader³  Gerald Assmann¹  Denise Buchner³  Yang Guo³  Andreas Ziesch³  Andreas Palagyi³  Stephanie Ochs³  Rüdiger P. Laubender⁴  Andreas Jung¹  Enrico N. De Toni³  Thomas Kirchner¹  Burkhard Göke³  Christiane Bruns² 

[1] Department of Pathology, Ludwig-Maximilians-University, Munich, Germany;Department of Surgery, Ludwig-Maximilians-University, Munich, Germany;Department of Medicine II, Ludwig-Maximilians-University, Munich, Germany;Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany;Department of Medicine II, Klinikum Neumarkt, Neumarkt i. d. OPf., Germany

关键词: HSP27;    biomarker;    gemcitabine;    pancreatic cancer;    TMA;   

DOI  :  10.1111/j.1582-4934.2011.01473.x

来源: Wiley

【 摘 要 】

Abstract

A role of heat shock protein 27 (HSP27) as a potential biomarker has been reported in various tumour entities, but comprehensive studies in pancreatic cancer are lacking. Applying tissue microarray (TMA) analysis, we correlated HSP27 protein expression status with clinicopathologic parameters in pancreatic ductal adenocarcinoma specimens from 86 patients. Complementary, we established HSP27 overexpression and RNA-interference models to assess the impact of HSP27 on chemo- and radiosensitivity directly in pancreatic cancer cells. In the TMA study, HSP27 expression was found in 49% of tumour samples. Applying univariate analyses, a significant correlation was found between HSP27 expression and survival. In the multivariate Cox-regression model, HSP27 expression emerged as an independent prognostic factor. HSP27 expression also correlated inversely with nuclear p53 accumulation, indicating either protein interactions between HSP27 and p53 or TP53 mutation-dependent HSP27-regulation in pancreatic cancer. In the sensitivity studies, HSP27 overexpression rendered HSP27 low-expressing PL5 pancreatic cancer cells more susceptible towards treatment with gemcitabine. Vice versa, HSP27 protein depletion in HSP27 high-expressing AsPC-1 cells caused increased gemcitabine resistance. Importantly, HSP27 expression was inducible in pancreatic cancer cell lines as well as primary cells. Taken together, our study suggests a role for HSP27 as a prognostic and predictive marker in pancreatic cancer. Assessment of HSP27 expression could thus facilitate the identification of specific patient subpopulations that might benefit from individualized treatment options. Additional studies need to clarify whether modulation of HSP27 expression could represent an attractive concept to support the incorporation of hyperthermia in clinical treatment protocols for pancreatic cancer.

【 授权许可】

Unknown   
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd