title: Identification of miR-139-5p as a saliva biomarker for tongue squamous cell carcinoma: a pilot study.
abstract: BACKGROUND
  Of all human oral carcinomas, 41 % are localized to the tongue. Despite considerable improvements in both diagnosis and treatment, tongue squamous cell carcinoma (TSCC) has remained one of the most lethal types of cancer. Here, we aimed at identifying a salivary microRNA (miRNA) expression signature specific for TSCC patients.
  
  
  METHODS
  To identify putative diagnostic biomarkers, we compared the miRNA expression profiles of saliva samples from three TSCC patients and four healthy control individuals using an Agilent miRNA microarray platform (V19). Three of the differentially expressed miRNAs identified were selected for further validation using quantitative reverse-transcription PCR (qRT-PCR) in saliva samples from 25 TSCC patients and 25 healthy control individuals.
  
  
  RESULTS
  Through microarray-based expression profiling, we found that 419 miRNAs were deregulated in the saliva samples from the TSCC patients compared to those from the healthy control individuals tested. Subsequent qRT-PCR analysis revealed that the expression level of miR-139-5p was significantly reduced in the TSCC validation samples compared to the controls. Further analysis of post-operative saliva samples derived from TSCC patients revealed that the miR-139-5p expression levels had turned back to normal again. In addition, we found that miR-139-5p exhibited enough power to discriminate pre-operative TSCC patients from both normal individuals (AUC: 0.805) and post-operative TSCC patients (AUC: 0.713), thereby underscoring its diagnostic potential.
  
  
  CONCLUSIONS
  From our results we conclude that saliva can be used as a feasible source for routine TSCC diagnostics and that miR-139-5p may serve as a potential biomarker for early TSCC detection.
authors.affiliation: Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey.
authors.forename: Mehmet Bugrahan
authors.initials: MB
authors.lastname: Duz
authors.affiliation: Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum, Turkey.
authors.forename: Omer Faruk
authors.initials: OF
authors.lastname: Karatas
authors.affiliation: Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey.|Departments of Medical Genetics and Molecular Biology and Genetics, Biruni University, 10. Yil Caddesi Protokol Yolu No: 45, 34010, Topkapi, Istanbul, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Guzel
authors.affiliation: Department of Otorhinolaryngology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Nesrettin Fatih
authors.initials: NF
authors.lastname: Turgut
authors.affiliation: Department of Otorhinolaryngology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yilmaz
authors.affiliation: Department of Medicine and Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey. mozen@bcm.edu.|Departments of Medical Genetics and Molecular Biology and Genetics, Biruni University, 10. Yil Caddesi Protokol Yolu No: 45, 34010, Topkapi, Istanbul, Turkey. mozen@bcm.edu.|Department of Pathology & Immunology Baylor College of Medicine, Houston, TX, 77030, USA. mozen@bcm.edu.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ozen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D012372:ROC Curve; D012463:Saliva / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C555098:MIRN139 microRNA, human; D035683:MicroRNAs
keywords: Biomarker; Microarray; Saliva; Tongue squamous cell carcinoma; miRNA