Page 115 - FINAL COMPENDIUM 2020-2021 27.2.2022

PREDICTING THE CLINICAL OUTCOME OF ORAL POTENTIALLY MALIGNANT DISORDERS
USING TRANSCRIPTOMIC-BASED MOLECULAR PATHOLOGY

Sathasivam HP, Kist R, Sloan P, Thomson P, Nugent M, Alexander J, Haider S, Robinson M
Objective: To develop and validate a gene expression signature that characterises oral
potentially malignant disorders (OPMD) with a high risk of undergoing malignant
transformation. Materials and methods: Patients with oral epithelial dysplasia at one
hospital were selected as the ‘training set’ (n = 56) whilst those at another hospital were
selected for the ‘test set’ (n = 66). RNA was extracted from formalin-fixed paraffin-
embedded (FFPE) diagnostic biopsies and analysed using the NanoString nCounter
platform. A targeted panel of 42 genes selected on their association with oral
carcinogenesis was used to develop a prognostic gene signature. Following data
normalisation, uni- and multivariable analysis, as well as prognostic modelling, were
employed to develop and validate the gene signature. A prognostic classifier composed
of 11 genes was developed using the training set. The multivariable prognostic model was
used to predict patient risk scores in the test set. Results: The prognostic gene signature
was an independent predictor of malignant transformation when assessed in the test set,
with the high-risk group showing worse prognosis [Hazard ratio = 12.65, p = 0.0003].
Conclusion: This study demonstrates proof of principle that RNA extracted from FFPE
diagnostic biopsies of OPMD, when analysed on the NanoString nCounter platform, can
be used to generate a molecular classifier that stratifies the risk of malignant
transformation with promising clinical utility.

Published in British Journal of Cancer volume 125, pages 413–421 (2021)

Dr Hans P Sathasivam Dr Michael Nugent
Institute for Medical Research Oral and Maxillofacial Surgery
National Institutes of Health Sunderland Royal Hospital
Ministry of Health Sunderland, 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 John Alexander
Newcastle Upon Tyne, UK Dr Syed Haider
The Breast Cancer Now Toby Robins Research Centre
Prof. Dr Peter Thomson The Institute of Cancer Research
Oral and Maxillofacial Surgery London, UK
Faculty of Dentistry
The University of Hong Kong
Hong Kong SAR

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