A novel approach for assessment of prostate cancer aggressiveness using survivin-driven tumour-activatable minicircles.,Gene Therapy

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A novel approach for assessment of prostate cancer aggressiveness using survivin-driven tumour-activatable minicircles.
Gene Therapy ( IF 4.6 ) Pub Date : 2019-03-13 , DOI: 10.1038/s41434-019-0067-6
TianDuo Wang _{1,

2} , Yuanxin Chen ₁ , John A Ronald _{1,

2,

3}

Affiliation

Early and accurate detection of cancer is essential to optimising patient outcomes. Of particular importance to prostate cancer is the ability to determine the aggressiveness of a primary tumour, which allows for effective management of patient care. In this work, we propose using gene vectors called tumour-activatable minicircles which deliver an exogenously encoded reporter gene into cancer cells, forcing them to produce a unique and sensitive biomarker. These minicircles express a blood reporter protein called secreted embryonic alkaline phosphatase mediated by the tumour-specific survivin promoter, which exhibits activity graded to prostate cancer aggressiveness. Together, these components underlie a detection system where levels of blood reporter are indicative of not only the presence, but also the metastatic potential of a tumour. Our goal was to assess the ability of tumour-activatable minicircles to detect and characterise primary prostate lesions. Our minicircles produced reporter levels related to survivin expression across a range of prostate cancer cell lines. When survivin-driven minicircles were administered intratumourally into mice, reporter levels in blood samples were significantly higher (p < 0.05) in mice carrying prostate tumours of high versus low-aggressiveness. Continued development of this gene-based system could provide clinicians with a powerful tool to evaluate prostate cancer aggressiveness using a sensitive and affordable blood assay.

中文翻译：

一种使用生存素驱动的肿瘤可激活小环评估前列腺癌侵袭性的新方法。

早期准确地检测癌症对于优化患者预后至关重要。对前列腺癌特别重要的是确定原发性肿瘤侵袭性的能力，这可以有效地管理患者护理。在这项工作中，我们建议使用称为肿瘤可激活小圆的基因载体，该载体将外源编码的报道基因传递到癌细胞中，迫使它们产生独特而敏感的生物标记。这些小圆圈表达了一种由肿瘤特异性survivin启动子介导的血液报告蛋白，称为分泌的胚胎碱性磷酸酶，其活性可分级为前列腺癌的侵袭性。这些组件共同构成了一个检测系统，在该系统中，血液报告分子的水平不仅指示肿瘤的存在，而且还指示其转移潜能。我们的目标是评估可肿瘤激活的小圆圈检测和表征原发性前列腺病变的能力。我们的小圆圈产生的报告基因水平与一系列前列腺癌细胞系中的survivin表达有关。当对小鼠进行瘤内存活蛋白驱动的小环时，携带高侵袭性和低侵袭性的前列腺肿瘤的小鼠血样中的报告基因水平显着更高（p <0.05）。这种基于基因的系统的持续开发可以为临床医生提供一种使用敏感且价格合理的血液分析方法评估前列腺癌侵袭性的强大工具。我们的小圆圈产生的报告基因水平与一系列前列腺癌细胞系中的survivin表达有关。当对小鼠进行瘤内存活蛋白驱动的小环时，携带高侵袭性和低侵袭性的前列腺肿瘤的小鼠血样中的报告基因水平显着更高（p <0.05）。这种基于基因的系统的持续开发可以为临床医生提供一种使用敏感且价格合理的血液分析方法评估前列腺癌侵袭性的强大工具。我们的小圆圈产生的报告基因水平与一系列前列腺癌细胞系中的survivin表达有关。当对小鼠进行瘤内存活蛋白驱动的小环时，携带高侵袭性和低侵袭性的前列腺肿瘤的小鼠血样中的报告基因水平显着更高（p <0.05）。这种基于基因的系统的持续开发可以为临床医生提供一种使用敏感且价格合理的血液分析方法评估前列腺癌侵袭性的强大工具。

更新日期：2019-11-18

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