Melbourne Dental School - Theses

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Subject: oral cancer × Author: Yap, Tami ×

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    Oral cancer prediction using microRNA in oral swirls
    Yap, Tami ( 2018)
    Purpose: To study a clinically convenient sample type, oral swirls as a source of microRNA for analysis in oral disease states. Objectives: To study a panel of OSCC-associated microRNA, identified in next generation sequencing (NGS) data of tissue specimens, in oral swirls from individuals with OSCC and oral potentially malignant disorders (OPMDs). Materials and Methods: Oral swirls were inspected using electron microscopy and tested for robustness by challenge with RNase and temperature shifts and analysis using microRNA by qPCR. Oral swirls were collected from 190 individuals with and without oral mucosal conditions. An OSCC- associated panel of microRNAs was identified in FFPE specimen NGS data and a fresh frozen specimen data set from The Cancer Genome Atlas. This panel was studied by qPCR in the oral swirls from 190 individuals with and without mucosal abnormalities including OSCC (n=53) and OPMDs (n=74). Results: Oral swirl sourced microRNA was consistently detected and demographics, comorbidities and oral disease states did not affect the yield of RNA. A reproducible workflow was used to extract RNA from oral swirls collected from 190 individuals. Upregulation of miR-31, miR-21 and downregulation of miR-99a, let-7c, miR-125b and miR-100 was found between OSCC and controls in NGS data of both FFPE and fresh frozen specimens. These microRNAs were studied in a training set of 15 OSCC vs 15 control oral swirls to develop a cumulative dysregulation score (AUC 0.95 (95% CI, 0.88-1.03)) and categorical algorithm-determined risk category. Utilizing the presence of HIGH-risk in 53 OSCC vs 54 controls, the test was 86.8% sensitive and 81.5% specific. One case of malignant transformation within the OPMD cohort demonstrated longitudinal utility of the test. Conclusion: Oral swirls provide a clinically convenient sample type for assessment of microRNA in disease states. This is first study to analyze microRNA sourced from oral swirls from individuals with and without mucosal abnormalities including OSCC and OPMDs. A HIGH-risk dysregulation signature was found to be accurate in indicating the presence of OSCC and exampled to parallel malignant transformation. Assessment in further longitudinal studies is warranted.