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Gene expression changes associated with malignant transformation of oral potentially malignant disorders

Lookup NU author(s): Dr Hans Sathasivam, John Casement, Professor Philip Sloan, Dr Max Robinson, Dr Ralf Kist

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Background: A large number of oral squamous cell carcinomas (OSCCs) are believed to be preceded by oral potentially malignant disorders (OPMD) that have an increased likelihood of malignant transformation compared to clinically normal mucosa. This study was performed to identify differentially expressed genes between OPMDs that underwent malignant transformation (MT) and those that did not, termed ‘non-transforming’ (NT) cases. Methods: Total RNA was extracted from formalin-fixed paraffin-embedded tissue biopsies of 20 OPMD cases with known clinical outcomes (10 MT vs. 10 NT). Samples were assessed for quantity, quality and integrity of RNA prior to sequencing. Analysis for differential gene expression between MT and NT was performed using statistical packages in R. Genes were considered to be significantly differentially expressed if the False Discovery Rate corrected p-value was < 0.05. Results: RNA yield was variable but RNA purity was good (A260/A280 >1.90). Analysis of RNA-Sequencing outputs revealed 41 genes (34 protein-coding; 7 non-coding) that were significantly differentially expressed between MT and NT cases. The log2 fold change for the statistically significant differentially expressed genes ranged from -2.63 to 2.48, with 23 protein-coding genes being downregulated and 11 protein-coding genes being upregulated in MT cases compared to NT cases.Conclusion: Several candidate genes that may play a role in malignant transformation of OPMD have been identified. Experiments to validate these candidates are underway. It is anticipated that this work will contribute to better understanding of the aetiopathogenesis of OPMD and development of novel biomarkers.


Publication metadata

Author(s): Sathasivam HP, Casement J, Bates T, Sloan P, Thomson P, Robinson M, Kist R

Publication type: Article

Publication status: Published

Journal: Journal of Oral Pathology & Medicine

Year: 2020

Issue: ePub ahead of Print

Online publication date: 02/08/2020

Acceptance date: 11/06/2020

Date deposited: 03/08/2020

ISSN (print): 0904-2512

ISSN (electronic): 1600-0714

Publisher: Wiley-Blackwell Publishing Ltd.

URL: https://doi.org/10.1111/jop.13090

DOI: 10.1111/jop.13090

PubMed id: 32740996


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