TY - JOUR
T1 - Cytoplasmic HuR Status Predicts Disease-free Survival in Resected Pancreatic Cancer
T2 - A Post-hoc Analysis from the International Phase III ESPAC-3 Clinical Trial
AU - Tatarian, Talar
AU - Jiang, Wei
AU - Leiby, Benjamin E.
AU - Grigoli, Amanda
AU - Jimbo, Masaya
AU - Dabbish, Nooreen
AU - Neoptolemos, John P.
AU - Greenhalf, William
AU - Costello, Eithne
AU - Ghaneh, Paula
AU - Halloran, Christopher
AU - Palmer, Daniel
AU - Buchler, Markus
AU - Yeo, Charles J.
AU - Winter, Jordan M.
AU - Brody, Jonathan R.
N1 - Publisher Copyright:
© Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - BIOMARKER
KW - ELAVL1
KW - European Study Group of Pancreatic Cancer
KW - HuR
KW - adjuvant therapy
KW - cancer
KW - pancreatic ductal adenocarcinoma
KW - resected pancreatic
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UR - http://www.scopus.com/inward/citedby.url?scp=84997769554&partnerID=8YFLogxK
U2 - 10.1097/SLA.0000000000002088
DO - 10.1097/SLA.0000000000002088
M3 - Article
C2 - 27893535
AN - SCOPUS:84997769554
SN - 0003-4932
VL - 267
SP - 364
EP - 369
JO - Annals of surgery
JF - Annals of surgery
IS - 2
ER -