title: Stromal microRNA-21 levels predict response to 5-fluorouracil in patients with pancreatic cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Donahue
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Nguyen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moughan
authors.forename: Luyi
authors.initials: L
authors.lastname: Li
authors.forename: Sergei
authors.initials: S
authors.lastname: Tatishchev
authors.forename: Paul
authors.initials: P
authors.lastname: Toste
authors.forename: James J
authors.initials: JJ
authors.lastname: Farrell
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D005472:Fluorouracil
keywords: 5-fluorouracil; biomarkers; microRNA-21; pancreatic cancer