MicroRNAs-208b-3p 204-5p 129-2-3p and 3065-5p as predictive markers of oral leukoplakia that progress to cancer

摘要

Leukoplakia is the most common precursor lesion of oral squamous cell carcinoma (OSCC). Currently, the risk of progression to OSCC is assessed based on histopathologic examination alone. However, this method fails to identify the subset of microscopically innocuous leukoplakia that ultimately transforms to OSCC. The aim of this study was to determine if microRNAs (miRNAs) can be utilized to identify non- and low-grade dysplastic oral lesions at risk for cancer progression. A retrospective study of genome-wide miRNA expression level analyses was performed in the training cohort (n=20) using deep sequencing formalin-fixed paraffin embedded incisional biopsy tissues from patients with oral leukoplakic lesions diagnosed with non- or low-grade dysplasia and known clinical outcome. The promising miRNA candidates were then evaluated in the validation cohort (n=80) using quantitative real-time PCR (qRT-PCR). Four promising miRNAs-208b-3p, 204-5p, 129-2-3p and 3065-5p were identified. Combining these four miRNAs as a panel with age and histologic diagnosis (p<0.004), our final model had a predictive value for the area under the receiver operating characteristic (ROC) curve (AUC) of 0.792, sensitivity of 76.9% and specificity of 73.7% to accurately identify non- and low-grade dysplastic lesions at risk of cancer progression, which is a significant improvement over histopathologic examination alone (AUC of 0.645). While further investigation is needed, discovery of predictive markers that can accurately identify histologically innocuous oral lesions at high risk for progression to OSSC will significantly improve clinical outcome by means of early intervention.