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The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of Oral Squamous Cell Carcinoma

ABSTRACT: Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programs. 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. 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 a third cohort using immunohistochemistry. In order to address the potential interest of the ectopic expressions as therapeutic targets, the transcriptome of OSCC cells in which one of the predictive marker genes, CCNA1, was inactivated was analysed by RNAseq. The genome-wide expression profile of an OSCC cell line, where CCNA1 had been inactivated was found similar to that of aggressive tumours positive for the three genes. The exploration of the whole gene expression profile characterizing aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Our experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting it could be a good target for therapeutic approaches.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171506 | GEO | 2021/07/20

REPOSITORIES: GEO

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