title: Heat shock protein 27 as a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma.
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.
authors: Department of Medicine II, Klinikum Neumarkt, Neumarkt id OPf, Germany.
authors: Claus
authors: C
authors: Schäfer
authors: Hendrik
authors: H
authors: Seeliger
authors: Dominik C
authors: DC
authors: Bader
authors: Gerald
authors: G
authors: Assmann
authors: Denise
authors: D
authors: Buchner
authors: Yang
authors: Y
authors: Guo
authors: Andreas
authors: A
authors: Ziesch
authors: Andreas
authors: A
authors: Palagyi
authors: Stephanie
authors: S
authors: Ochs
authors: Rüdiger P
authors: RP
authors: Laubender
authors: Andreas
authors: A
authors: Jung
authors: Enrico N
authors: EN
authors: De Toni
authors: Thomas
authors: T
authors: Kirchner
authors: Burkhard
authors: B
authors: Göke
authors: Christiane
authors: C
authors: Bruns
authors: Eike
authors: E
authors: Gallmeier
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D018869:Heat-Shock Response / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D015999:Multivariate Analysis; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D046888:Tissue Array Analysis; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D003841:Deoxycytidine; D000093542:Gemcitabine