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

• Published in: Clinical biochemistry Vol. 48; no. 3; pp. 115 - 121
• Main Authors: Lu, Ya-Ching, Chang, Joseph Tung-Chieh, Huang, Yu-Chen, Huang, Chi-Che, Chen, Wen-Ho, Lee, Li-Yu, Huang, Bing-Shen, Chen, Yin-Ju, Li, Hsiao-Fang, Cheng, Ann-Joy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2015
• Subjects: Adult; Aged; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Circulating miRNA; Cold Temperature; Early detection; Early Detection of Cancer; Female; Gene Expression Regulation, Neoplastic; Humans; Logistic Models; Male; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miR-196a; miR-196b; Mouth Neoplasms - blood; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Oral cancer; Precancerous Conditions - blood; Precancerous Conditions - genetics; Preservation, Biological; RNA Stability - genetics; ROC Curve; Sensitivity and Specificity; Young Adult; Oral cancer; Circulating miRNA; miR-196b; Early detection; miR-196a
• ISSN: 0009-9120; 1873-2933; 1873-2933
• DOI: 10.1016/j.clinbiochem.2014.11.020

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. 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. 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%). Combined determination of circulating miR-196a and miR-196b levels may serve as panel plasma biomarkers for the early detection of oral cancer. •miR-196a/b are elevated in the plasma of oral cancer and pre-cancer patients.•The elevations of miR-196a/b in oral cancer patients are associated with T stage.•miR-196a provides excellent specificity for the diagnosis of oral malignancy.•miR-196b provides super sensitivity for the screening of oral malignancy.•Panel miR-196s serve as excellent biomarkers for early detection of oral cancer.