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Stromal MicroRNA‐21 levels predict response to 5‐fluorouracil in patients with pancreatic cancer
Author(s) -
Donahue Timothy R.,
Nguyen Andrew H.,
Moughan Jennifer,
Li Luyi,
Tatishchev Sergei,
Toste Paul,
Farrell James J.
Publication year - 2014
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23750
Subject(s) - medicine , gemcitabine , oncology , hazard ratio , stromal cell , pancreatic cancer , proportional hazards model , cancer , confidence interval , cancer research
Background and Objectives MicroRNA‐21 (miR‐21) is upregulated and inversely associated with survival in many cancer types, including pancreatic ductal adenocarcinoma (PDAC). We studied the predictive value of miR‐21 levels for gemcitabine or 5‐fluorouracil (5‐FU) response in tumor cells (TCs) or cancer associated fibroblasts (CAFs) in a cohort of PDAC patients from the RTOG 9704 trial. Methods MiR‐21 expression in CAFs and TCs, determined by in situ hybridization, of the 229 PDAC subset from RTOG 9704 was correlated with (i) histopathology characteristics using a chi‐square test; and (ii) patient overall survival (OS) using the Cox proportional hazards model. Results MiR‐21 was strongly expressed in TCs and CAFs in 137/182 (75%) and 152/181 (84%) PDACs, respectively. MiR‐21 expression in CAFs for the group given 5‐FU for OS: (i) approached significance in a univariate analysis (hazard ratio [HR], 1.57; 95% confidence interval [CI], 0.95–2.57; P = 0.07); and (ii) was significant in the multivariate model (HR, 1.70; 95% CI, 1.03–2.82; P = 0.038). Conclusions MiR‐21 expression in CAFs was associated with decreased OS in PDAC patients who received 5‐FU, but not gemcitabine. These findings begin to identify stromal miR‐21 as a marker to guide chemotherapy choice in PDAC patients. J. Surg. Oncol. 2014; 110:952–959 . © 2014 Wiley Periodicals, Inc.