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

Sathasivam, Hans P., Casement, John, Bates, Timothy, Sloan, Philip, Thomson, Peter, Robinson, Max, and Kist, Ralf (2021) Gene expression changes associated with malignant transformation of oral potentially malignant disorders. Journal of Oral Pathology and Medicine, 50 (1). pp. 60-67.

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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 etiopathogenesis of OPMD and development of novel biomarkers.

Item ID: 68421
Item Type: Article (Research - C1)
ISSN: 1600-0714
Keywords: malignant transformation, oral potentially malignant disorders, oral squamous cell carcinoma, RNA-Sequencing
Copyright Information: © 2020 The Authors. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Funders: Newcastle upon Tyne Hospitals NHS Charity
Projects and Grants: Grant Number: BH102216
Date Deposited: 22 Jun 2021 23:35
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321103 Cancer genetics @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3203 Dentistry > 320307 Oral medicine and pathology @ 50%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 50%
20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 50%
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