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

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

PROVIDER: PRJNA719820 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14145557.fastq.gz	Fastqsanger.gz
	SRR14145558.fastq.gz	Fastqsanger.gz
	SRR14145559.fastq.gz	Fastqsanger.gz
	SRR14145560.fastq.gz	Fastqsanger.gz
	SRR14145561.fastq.gz	Fastqsanger.gz

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The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma.

Project description:BackgroundLarge-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.MethodsA 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.ResultsA 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.DiscussionThe 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.

| S-EPMC8505643 | biostudies-literature

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

Project description: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.

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