title: MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder.
abstract: OBJECTIVE
  MicroRNAs (miRNAs, miRs) have shown diagnostic and prognostic potential for oral cancer but their role in oral potentially malignant disorder (OPMD) has been less investigated. We aimed to assess whether miR-21 and miR-31, two of the most relevant miRNAs in oral cancer, are useful as prognostic factors for OPMD progression.
  
  
  METHODS
  miR-21 and miR-31 in 20 saliva samples and 46 tissue samples from patients with OPMD (mean follow-up of 820days) were analyzed by quantitative reverse transcription PCR and in situ hybridization, respectively. The log-rank test, receiver operating characteristic curve, and Kaplan-Meier disease free survival analysis were used to assess the correlation between miRNA levels and OPMD progression.
  
  
  RESULTS
  Significantly increased salivary miR-21 and miR-31 expression (P=0.003 and P<0.001, respectively) was observed in patients with OPMD compared to control individuals. Patients with recurrent OPMD and/or malignant transformation exhibited a further augmented expression of miR-31, but not miR-21, in the epithelium. Furthermore, increased miR-31 expression as well as epithelial dysplasia is an independent risk factor for OPMD progression as demonstrated in Cox-proportional hazard model (HR: 8.43, P<0.05, 95%CI: 1.04 to 68.03).
  
  
  CONCLUSIONS
  Salivary miR-21 and miR-31 are applicable as useful OPMD screening tools. Epithelial dysplasia and miR-31 up-regulation synergistically predict the increased incidence of recurrence and/or malignant transformation in patients with OPMD. Detection of miR-31 expression is an adjuvant method for screening of high-risk OPMD.
authors.affiliation: Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Hung
authors.affiliation: Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Dentistry, Taipei MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chung-Ji
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Department of Dentistry, National Yang-Ming University Hospital, I-Lan, Taiwan.
authors.forename: Peng-Chih
authors.initials: PC
authors.lastname: Chiu
authors.affiliation: Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Dentistry, Taipei MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Jiun-Sheng
authors.initials: JS
authors.lastname: Lin
authors.affiliation: Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Chang
authors.affiliation: Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Shih
authors.affiliation: Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: sykao@vghtpe.gov.tw.
authors.forename: Shou-Yen
authors.initials: SY
authors.lastname: Kao
authors.affiliation: Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan; Department of Dentistry, National Yang-Ming University Hospital, I-Lan, Taiwan. Electronic address: hftu@ym.edu.tw.
authors.forename: Hsi-Feng
authors.initials: HF
authors.lastname: Tu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012463:Saliva / Q000737:chemistry
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: Carcinogenesis; Malignant; Marker; MicroRNA; OPMD; Saliva; miR-31