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

OBJECTIVES: The 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 METHODS: To 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.

RESULTS: In 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%).

CONCLUSION: Combined determination of circulating miR-196a and miR-196b levels may serve as panel plasma biomarkers for the early detection of oral cancer.