MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder

Abstract

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. 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. 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). 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.