title: MicroRNA-100 and microRNA-21 as markers of survival and chemotherapy response in pancreatic ductal adenocarcinoma UICC stage II.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) remains a highly chemoresistant tumor entity for which no reliable molecular targets exist to predict or influence the success of chemotherapy. Recently, we identified a panel of microRNAs associated with induced gemcitabine chemoresistance in human PDAC cell lines. This clinical study evaluates these microRNAs and associated molecular markers as prognostic markers of outcome in 98 PDAC patients Union Internationale Contre le Cancer (UICC) stage II undergoing curative surgery with adjuvant gemcitabine chemotherapy. The primary end points of this study are recurrence-free survival and overall survival.
  
  
  RESULTS
  Poor response to chemotherapy was significantly correlated to overexpression of microRNA-21 (p = 0.029), microRNA-99a (p = 0.037), microRNA-100 (p = 0.028), and microRNA-210 (p = 0.021) in tissue samples of PDAC patients UICC stage II. Upregulation of these microRNAs was associated with a significantly shorter overall survival and recurrence-free survival (p < 0.05). Overexpression of phosphatase and tensin homolog (PTEN) (p = 0.039) and low expression of multidrug resistance (MDR)-1 (p = 0.043) and breast cancer resistance protein (BCRP)-1 (p = 0.038) were significantly correlated to improved response to adjuvant chemotherapy. Adjuvant gemcitabine treatment (p < 0.0001) and low tumor grading (p = 0.047) were correlated to better outcome. MicroRNA-100, microRNA-21, and its targets PTEN and MDR-1 were independent factors of survival in multivariate analysis.
  
  
  CONCLUSIONS
  Multivariate survival analyses identified microRNA-21 and microRNA-100 as unfavorable prognostic factors in resected and adjuvant treated PDAC UICC stage II patients.
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, Germany.
authors.forename: Sameer Abdallah
authors.initials: SA
authors.lastname: Dhayat
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, Germany.
authors.forename: Baha
authors.initials: B
authors.lastname: Abdeen
authors.affiliation: Department of Pathology, University Hospital Muenster, Albert-Schweitzer-Campus 1 (D17), 48149 Muenster, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köhler
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Senninger
authors.affiliation: Comprehensive Cancer Center Muenster, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Haier
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1 (W1), 48149 Muenster, Germany.
authors.forename: Wolf Arif
authors.initials: WA
authors.lastname: Mardin
keywords: Chemoresistance; Pancreatic ductal adenocarcinoma; microRNA