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

Clin Biochem. 2015 Feb;48(3):115-21. doi: 10.1016/j.clinbiochem.2014.11.020. Epub 2014 Dec 5.

Abstract

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.

Keywords: Circulating miRNA; Early detection; Oral cancer; miR-196a; miR-196b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Cold Temperature
  • Early Detection of Cancer*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Logistic Models
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics*
  • Middle Aged
  • Mouth Neoplasms / blood*
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Precancerous Conditions / blood
  • Precancerous Conditions / genetics
  • Preservation, Biological
  • RNA Stability / genetics
  • ROC Curve
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MIRN196 microRNA, human
  • MicroRNAs