Page 118 - FINAL COMPENDIUM 2020-2021 27.2.2022

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 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 etiopathogenesis of OPMD and development of novel
biomarkers.

Published in J Oral Pathol Med. 2021; 50: 60– 67. https://doi.org/10.1111/jop.13090

Dr Hans P Sathasivam John Casement
Institute for Medical Research Bioinformatics Support Unit
National Institutes of Health Newcastle University
Ministry of Health Newcastle upon Tyne, UK
Malaysia
Dr Max Robinson
Dr Ralf Kist Department of Cellular Pathology
Prof Dr Philip Sloan Newcastle University, UK.
Newcastle University Biosciences Institute
Newcastle University Centre for Cancer Dr Timothy Bates
Newcastle upon Tyne, UK Department of Pathology
Queen Elizabeth Hospital Birmingham
Prof. Dr Peter Thomson University Hospitals Birmingham
Oral and Maxillofacial Surgery Birmingham, UK
Faculty of Dentistry
The University of Hong Kong
Hong Kong, Hong Kong SAR

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