title: Discovery and prevalidation of salivary extracellular microRNA biomarkers panel for the noninvasive detection of benign and malignant parotid gland tumors.
abstract: OBJECTIVE
  This study was conducted to explore the differences in salivary microRNA (miRNA) profiles between patients with malignant or benign parotid gland tumors as a potential preoperative diagnostic tool of tumors in the salivary glands.
  
  
  METHODS
  Whole saliva samples from patients with malignant (n = 38) or benign (n = 29) parotid gland tumors were obtained from the Salivary Gland Tumor Biorepository (SGTB). After total RNA isolation, human miRNA cards were used for miRNA profiling. The differential miRNA expression was analyzed using two-sided Wilcoxon test. Quantitative real-time PCR (qRT-PCR) was used to validate selected miRNAs in an independent sample set. Receiver-operating characteristics curve and probability of malignancy was exploited to evaluate the diagnostic power of the validated miRNAs.
  
  
  RESULTS
  With miRNA profiling, 57 of 750 investigated miRNAs were differently expressed, of which 54 showed higher miRNA expression in samples from patients with malignant tumors than those from patients with benign tumors. Validating the expression in an independent sample set of 9 miRNAs revealed indeed higher expression of miRNAs in malignant samples compared with benign samples. The expression of 6 validated miRNAs was statistically significantly different between the two groups (P < 0.05). A four miRNA combination was able to discriminate between saliva samples from patients with malignant tumors from those of patients with benign parotid gland tumors (sensitivity 69%, specificity 95%).
  
  
  CONCLUSIONS
  Salivary miRNA profiles differ in saliva from patients with malignant from saliva from patients with a benign parotid gland tumor. These preliminary results are promising to develop a noninvasive diagnostic tool for diagnosing tumors in the salivary glands.
authors.affiliation: Department of Oral and Maxillofacial Surgery and Oral Pathology, Academic Centre for Dentistry Amsterdam/VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Matse
authors.forename: Janice
authors.initials: J
authors.lastname: Yoshizawa
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Jan G M
authors.initials: JG
authors.lastname: Bolscher
authors.forename: Enno C I
authors.initials: EC
authors.lastname: Veerman
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bloemena
authors.forename: David T W
authors.initials: DT
authors.lastname: Wong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D005110:Extracellular Space; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010307:Parotid Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D012372:ROC Curve; D015203:Reproducibility of Results; D012463:Saliva / Q000737:chemistry
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs