Stromal MicroRNA-21 Levels Predict Response to 5-Fluorouracil in Patients With Pancreatic Cancer

Background and ObjectivesMicroRNA-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. MethodsMiR-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. ResultsMiR-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). ConclusionsMiR-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. (c) 2014 Wiley Periodicals, Inc.