Cytoplasmic HuR Status Predicts Disease-free Survival in Resected Pancreatic Cancer: A Post-hoc Analysis from the International Phase III ESPAC-3 Clinical Trial

Talar Tatarian, Wei Jiang, Benjamin E. Leiby, Amanda Grigoli, Masaya Jimbo, Nooreen Dabbish, John P. Neoptolemos, William Greenhalf, Eithne Costello, Paula Ghaneh, Christopher Halloran, Daniel Palmer, Markus Buchler, Charles J. Yeo, Jordan M. Winter, Jonathan R. Brody

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Objectives: 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. Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)364-369
Number of pages6
JournalAnnals of surgery
Volume267
Issue number2
DOIs
StatePublished - Feb 1 2018
Externally publishedYes

Keywords

  • BIOMARKER
  • ELAVL1
  • European Study Group of Pancreatic Cancer
  • HuR
  • adjuvant therapy
  • cancer
  • pancreatic ductal adenocarcinoma
  • resected pancreatic

ASJC Scopus subject areas

  • Surgery

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