title: Prognostic value of the MicroRNA regulators Dicer and Drosha in non-small-cell lung cancer: co-expression of Drosha and miR-126 predicts poor survival.
abstract: BACKGROUND
  Dicer and Drosha are important enzymes for processing microRNAs. Recent studies have exhibited possible links between expression of different miRNAs, levels of miRNA processing enzymes, and cancer prognosis. We have investigated the prognostic impact of Dicer and Drosha and their correlation with miR-126 expression in a large cohort of non-small cell lung cancer (NSCLC) patients. We aimed to find patient groups within the cohort that might have an advantage of receiving adjunctive therapies.
  
  
  METHODS
  Dicer expression in the cytoplasm and Drosha expression in the nucleus were evaluated by manual immunohistochemistry of tissue microarrays (TMAs), including tumor tissue samples from 335 patients with resected stages I to IIIA NSCLC. In addition, in situ hybridizations of TMAs for visualization of miR-126 were performed. Kaplan-Meier analysis was performed, and the log-rank test via SPSS v.22 was used for estimating significance levels.
  
  
  RESULTS
  In patients with normal performance status (ECOG = 0, n = 197), high Dicer expression entailed a significantly better prognosis than low Dicer expression (P = 0.024). Dicer had no significant prognostic value in patients with reduced performance status (ECOG = 1-2, n = 138). High Drosha expression was significantly correlated with high levels of the microRNA 126 (miR-126) (P = 0.004). Drosha/miR-126 co-expression had a significant negative impact on the disease-specific survival (DSS) rate (P < 0.001). Multivariate analyses revealed that the interaction Dicer*Histology (P = 0.049) and Drosha/miR-126 co-expression (P = 0.033) were independent prognostic factors.
  
  
  CONCLUSIONS
  In NSCLC patients with normal performance status, Dicer is a positive prognostic factor. The importance of Drosha as a prognostic factor in our material seems to be related to miR-126 and possibly other microRNAs.
authors.affiliation: Department of Clinical Pathology, University Hospital of Northern Norway, N-9038 Tromsø, Norway ; Department of Medical Biology, Tromsø, Norway.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lønvik
authors.affiliation: Department of Clinical Pathology, University Hospital of Northern Norway, N-9038 Tromsø, Norway.
authors.forename: Sveinung W
authors.initials: SW
authors.lastname: Sørbye
authors.affiliation: Department of Medical Biology, Tromsø, Norway.
authors.forename: Marit N
authors.initials: MN
authors.lastname: Nilsen
authors.affiliation: Department of Clinical Medicine, UiT - The Arctic University of Norway, N-9037 Tromsø, Norway.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Paulssen
keywords: Dicer; Drosha; Immunohistochemistry; NSCLC; miR-126; microRNA