Mehmet Bugrahan Duz1, Omer Faruk Karatas2, Esra Guzel1,3, Nesrettin Fatih Turgut4, Mehmet Yilmaz4, Chad J Creighton5, Mustafa Ozen6,7,8. 1. Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey. 2. Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum, Turkey. 3. Departments of Medical Genetics and Molecular Biology and Genetics, Biruni University, 10. Yil Caddesi Protokol Yolu No: 45, 34010, Topkapi, Istanbul, Turkey. 4. Department of Otorhinolaryngology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. 5. Department of Medicine and Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX, USA. 6. Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey. mozen@bcm.edu. 7. 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. 8. Department of Pathology & Immunology Baylor College of Medicine, Houston, TX, 77030, USA. mozen@bcm.edu.
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.
BACKGROUND: Of all humanoral 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.
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