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.

中文翻译：

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双调蛋白、细胞周期蛋白 A1 和 DDX20/Gemin3 表达的联合检测预测口腔鳞状细胞癌的侵袭性形式

背景

大规模的遗传和表观遗传失调使癌细胞能够异位激活组织特异性表达程序。一种专门设计的策略应用于口腔鳞状细胞癌 (OSCC)，以检测异位基因激活并开发预后分层测试。

方法

使用 OSCC 的全基因组转录组数据（包括训练和验证队列）实施了一种专门的原始预后生物标志物发现方法。系统地检测沉默基因的异常表达，与生存概率相关，并作为预测性生物标志物进行评估。使用免疫组织化学在独立队列中证实了由此产生的分层测试。

结果

在单变量和多变量分析中发现特定基因表达特征，包括三个基因AREG、CCNA1和DDX20的组合与高风险 OSCC 相关。它被转化为基于免疫组织化学的测试，成功地对我们自己的独立队列中的患者进行了分层。

讨论

对表征侵袭性 OSCC 肿瘤的整个基因表达谱的探索突出了它们增强的增殖和低分化的内在性质。OSCC 细胞中CCNA1的实验性靶向与转录组特征向侵袭性较低的 OSCC 形式的转变有关，这表明 CCNA1 可能是治疗方法的良好靶点。