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The Combined Detection of Amphiregulin, Cyclin A1 and Ddx20/Gemin3 Expression Predicts Aggressive Forms of Oral Squamous Cell Carcinoma Publisher Pubmed



Bourovaflin E1 ; Derakhshan S2 ; Goudarzi A3 ; Wang T1 ; Vitte AL1 ; Chuffart F1 ; Khochbin S1 ; Rousseaux S1 ; Aminishakib P2, 4
Authors
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Authors Affiliations
  1. 1. CNRS UMR 5309/INSERM U1209/University Grenoble-Alpes/Institute for Advanced Biosciences, La Tronche, France
  2. 2. Oral and Maxillofacial Pathology Department, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Cancer Institute Hospital, IKHC, Tehran University of Medical Sciences, Tehran, Iran

Source: British Journal of Cancer Published:2021


Abstract

Background: Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. Methods: A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. Results: A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. Discussion: The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches. © 2021, The Author(s).