title: Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer.
abstract: OBJECTIVE
  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.
  
  
  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%).
  
  
  CONCLUSIONS
  Combined determination of circulating miR-196a and miR-196b levels may serve as panel plasma biomarkers for the early detection of oral cancer.
authors.affiliation: Department of Medical Biotechnology, Medical College, Chang Gung University, 259 Wen-Hwa 1st Road, Taoyuan 333, Taiwan.
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital, Chang Gung University, 5. Fu-Hsing Street. Kuei-Shan, Taoyuan 333, Taiwan.
authors.forename: Joseph Tung-Chieh
authors.initials: JT
authors.lastname: Chang
authors.affiliation: Department of Oral Maxillofacial Surgery, Chang Gung Memorial Hospital, 5. Fu-Hsing Street. Kuei-Shan, Taoyuan 333, Taiwan.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, 5. Fu-Hsing Street. Kuei-Shan, Taoyuan 333, Taiwan.
authors.forename: Chi-Che
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Oral Maxillofacial Surgery, Chang Gung Memorial Hospital, 5. Fu-Hsing Street. Kuei-Shan, Taoyuan 333, Taiwan.
authors.forename: Wen-Ho
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, 259 Wen-Hwa 1st Road, Taoyuan 333, Taiwan.
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Chang Gung Memorial Hospital, Chang Gung University, 5. Fu-Hsing Street. Kuei-Shan, Taoyuan 333, Taiwan.
authors.forename: Bing-Shen
authors.initials: BS
authors.lastname: Huang
authors.affiliation: Department of Medical Biotechnology, Medical College, Chang Gung University, 259 Wen-Hwa 1st Road, Taoyuan 333, Taiwan.
authors.forename: Yin-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Medical Biotechnology, Medical College, Chang Gung University, 259 Wen-Hwa 1st Road, Taoyuan 333, Taiwan.
authors.forename: Hsiao-Fang
authors.initials: HF
authors.lastname: Li
authors.affiliation: Department of Medical Biotechnology, Medical College, Chang Gung University, 259 Wen-Hwa 1st Road, Taoyuan 333, Taiwan. Electronic address: ajchen@mail.cgu.edu.tw.
authors.forename: Ann-Joy
authors.initials: AJ
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D003080:Cold Temperature; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000097:blood / Q000235:genetics; D011309:Preservation, Biological; D020871:RNA Stability / Q000235:genetics; D012372:ROC Curve; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C542543:MIRN196 microRNA, human; D035683:MicroRNAs
keywords: Circulating miRNA; Early detection; Oral cancer; miR-196a; miR-196b