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GENE EXPRESSION CHANGES ASSOCIATED WITH MALIGNANT TRANSFORMATION OF
ORAL POTENTIALLY MALIGNANT DISORDERS

Sathasivam HP, Casement J, Bates T, Sloan P, Thomson P, Robinson M, Kist R

Introduction: 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. Objective: To identify
differentially expressed genes between OPMDs that underwent malignant transformation
(MT) and those that did not, termed “non-transforming” (NT) cases. Materials and
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 down regulated and 11 protein-coding genes
being up regulated 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 etiopathogenesis of OPMD and development of
novel biomarkers.

Published in Journal of Oral Pathology & Medicine, 2021;50:60–67. https://doi.org/10.1111/jop.13090. Epub 2020 August 2

Dr Hans Prakash Sathasivam Prof Dr Philip Sloan
Cancer Research Centre Dr Max Robinson
Institute for Medical Research Newcastle upon Tyne Hospital NHS Foundation Trust
National Institutes of Health Newcastle upon Tyne UK
Setia Alam, Malaysia
Dr John Casement Dr Peter Thomson
Bioinformatics Support Unit Oral and Maxillofacial Surgery
Newcastle University Faculty of Dentistry
Newcastle upon Tyne UK The University of Hong Kong
Hong Kong SAR Hong Kong

Dr Timothy Bates Dr Ralf Kist
Queen Elizabeth Hospital Newcastle University Biosciences Institute
Birmingham UK Newcastle University Centre for Cancer
Newcastle upon Tyne UK

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