title: Cytoplasmic HuR Status Predicts Disease-free Survival in Resected Pancreatic Cancer: A Post-hoc Analysis From the International Phase III ESPAC-3 Clinical Trial.
abstract: We tested cytoplasmic HuR (cHuR) as a predictive marker for response to chemotherapy by examining tumor samples from the international European Study Group of Pancreatic Cancer-3 trial, in which patients with resected pancreatic ductal adenocarcinoma (PDA) received either gemcitabine (GEM) or 5-fluorouracil (5-FU) adjuvant monotherapy.
  
  
  
  Previous studies have implicated the mRNA-binding protein, HuR (ELAVL1), as a predictive marker for PDA treatment response in the adjuvant setting. These studies were, however, based on small cohorts of patients outside of a clinical trial, or a clinical trial in which patients received multimodality therapy with concomitant radiation.
  
  
  
  Tissue samples from 379 patients with PDA enrolled in the European Study Group of Pancreatic Cancer-3 trial were immunolabeled with an anti-HuR antibody and scored for cHuR expression. Patients were dichotomized into groups of high versus low cHuR expression.
  
  
  
  There was no association between cHuR expression and prognosis in the overall cohort [disease-free survival (DFS), P = 0.44; overall survival, P = 0.41). Median DFS for patients with high cHuR was significantly greater for patients treated with 5-FU compared to GEM [20.1 months, confidence interval (CI): 8.3-36.4 vs 10.9 months, CI: 7.5-14.2; P = 0.04]. Median DFS was similar between the treatment arms in patients with low cHuR (5-FU, 12.8 months, CI: 10.6-14.6 vs GEM, 12.9 months, CI: 11.2-15.4).
  
  
  
  Patients with high cHuR-expressing tumors may benefit from 5-FU-based adjuvant therapy as compared to GEM, whereas those patients with low cHuR appear to have no survival advantage with GEM compared with 5-FU. Further studies are needed to validate HuR as a biomarker in both future monotherapy and multiagent regimens.
authors.affiliation: Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Talar
authors.initials: T
authors.lastname: Tatarian
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Leiby
authors.affiliation: Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Grigoli
authors.affiliation: Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Masaya
authors.initials: M
authors.lastname: Jimbo
authors.affiliation: Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Nooreen
authors.initials: N
authors.lastname: Dabbish
authors.affiliation: Institute of Translational Medicine, Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Neoptolemos
authors.affiliation: Institute of Translational Medicine, Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK.
authors.forename: William
authors.initials: W
authors.lastname: Greenhalf
authors.affiliation: Institute of Translational Medicine, Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK.
authors.forename: Eithne
authors.initials: E
authors.lastname: Costello
authors.affiliation: Institute of Translational Medicine, Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Ghaneh
authors.affiliation: Institute of Translational Medicine, Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Halloran
authors.affiliation: Institute of Translational Medicine, Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Palmer
authors.affiliation: Department of Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Buchler
authors.affiliation: Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.affiliation: Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Winter
authors.affiliation: Jefferson Pancreas, Biliary, and Related Cancer Center, Department of Surgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brody
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003593:Cytoplasm / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine