Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer

Abstract

ObjectivesThe aim of this study was to determine whether the oncogenic microRNA family members miR-196a and miR-196b can be circulating biomarkers for the early detection of oral cancer. Design and methodsTo determine the stability of circulating miRNA, the blood sample was aliquot and stored at different temperature conditions for analysis. To assess the diagnostic efficacy, we determined the levels of miR-196s in plasma samples, including 53 from healthy individuals, 16 from pre-cancer patients, and 90 from oral cancer patients. ResultsIn general, circulating miRNA was very stable when storing plasma samples at -20°C or below. In clinical study, both circulating miR-196a and miR-196b were substantially up-regulated in patients with oral pre-cancer lesions (5.9- and 14.8-fold, respectively; P<0.01), as well as in oral cancer patients (9.3- and 17.0-fold, respectively; P<0.01). These results show prominent discrimination between normal and pre-cancer patients (AUC=0.764 or 0.840, miR-196a or miR-196b, respectively), and between normal and cancer patients (AUC=0.864 or 0.960, miR-196a or miR-196b, respectively). The combined determination of miR-196a and miR-196b levels produces excellent sensitivity and specificity in the diagnosis of patients with oral pre-cancer (AUC=0.845) or oral cancer (AUC=0.963), as well as in the prediction of potential malignancy (AUC=0.950, sensitivity=91%, specificity=85%). ConclusionCombined determination of circulating miR-196a and miR-196b levels may serve as panel plasma biomarkers for the early detection of oral cancer.