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

Br J Cancer. 2021 Oct;125(8):1122-1134. doi: 10.1038/s41416-021-01491-x. Epub 2021 Jul 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphiregulin / genetics*
  • Amphiregulin / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cyclin A1 / genetics*
  • Cyclin A1 / metabolism
  • DEAD Box Protein 20 / genetics*
  • DEAD Box Protein 20 / metabolism
  • Data Mining
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Male
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Retrospective Studies
  • Sequence Analysis, RNA
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / pathology*


  • AREG protein, human
  • Amphiregulin
  • Biomarkers, Tumor
  • CCNA1 protein, human
  • Cyclin A1
  • DDX20 protein, human
  • DEAD Box Protein 20