title: A low Dicer expression is associated with resistance to 5-FU-based chemoradiotherapy and a shorter overall survival in patients with oral squamous cell carcinoma.
abstract: BACKGROUND
  The deregulation of microRNA (miRNA) is associated with multiple processes involved in cancer progression. RNase III endonucleases, Dicer and Drosha, are key enzymes for miRNA biogenesis, and it has been reported that altered expressions of these molecules affect the clinical outcomes of patients with various cancers. However, the clinical value of measuring the levels of Dicer and Drosha in oral squamous cell carcinoma (OSCC) patients is unclear. The purpose of this study was to determine the clinical significance of the expressions of Dicer and Drosha in patients with OSCC.
  
  
  METHODS
  Oral squamous cell carcinoma specimens were obtained from 61 patients who underwent surgery following 5-fluorouracil-based chemoradiotherapy at Kumamoto University Hospital between October 2003 and January 2009. Paraffin-embedded sections obtained from biopsy specimens were immunohistochemically analyzed. The associations between Dicer, Drosha, and various clinicopathological features were examined, and the effects of Dicer and Drosha on the prognosis were evaluated.
  
  
  RESULTS
  A low Dicer tumor expression was significantly correlated with the pathological response to chemoradiotherapy. Furthermore, a Cox regression analysis based on the overall survival revealed the Dicer expression status (hazard ratio, 0.34; P = 0.048) and pathological response to chemoradiotherapy (hazard ratio, 0.21; P = 0.014) to be significant prognostic factors in OSCC patients. On the other hand, the Drosha expression was not associated with any clinicopathological features or the prognosis.
  
  
  CONCLUSIONS
  These results suggest that Dicer is a potential biomarker for predicting the clinical response to 5-FU-based chemoradiotherapy and the overall survival in patients with OSCC.
authors: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors: Kenta
authors: K
authors: Kawahara
authors: Hideki
authors: H
authors: Nakayama
authors: Masashi
authors: M
authors: Nagata
authors: Ryoji
authors: R
authors: Yoshida
authors: Akiyuki
authors: A
authors: Hirosue
authors: Takuya
authors: T
authors: Tanaka
authors: Yoshihiro
authors: Y
authors: Nakagawa
authors: Yuichiro
authors: Y
authors: Matsuoka
authors: Taku
authors: T
authors: Kojima
authors: Yasuo
authors: Y
authors: Takamune
authors: Yoshihiro
authors: Y
authors: Yoshitake
authors: Akimitsu
authors: A
authors: Hiraki
authors: Masanori
authors: M
authors: Shinohara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D059248:Chemoradiotherapy; D053487:DEAD-box RNA Helicases / Q000032:analysis*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D043244:Ribonuclease III / Q000032:analysis*; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D005472:Fluorouracil
keywords: Dicer; microRNA; oral squamous cell carcinoma; prognosis; resistance