BACKGROUND Despite the progress in neuroblastoma therapies the mortality of high-risk patients is still high (40-50%) and the molecular basis of the disease remains poorly known. Recently, a mathematical model was used to demonstrate that the network regulating stress signaling by the c-Jun N-terminal kinase pathway played a crucial role in survival of patients with neuroblastoma irrespective of their MYCN amplification status. This demonstrates the enormous potential of computational models of biological modules for the discovery of underlying molecular mechanisms of diseases. RESULTS Since signaling is known to be highly relevant in cancer, we have used a computational model of the whole cell signaling network to understand the molecular determinants of bad prognostic in neuroblastoma. Our model produced a comprehensive view of the molecular mechanisms of neuroblastoma tumorigenesis and progression. CONCLUSION We have also shown how the activity of signaling circuits can be considered a reliable model-based prognostic biomarker. REVIEWERS This article was reviewed by Tim Beissbarth, Wenzhong Xiao and Joanna Polanska. For the full reviews, please go to the Reviewers' comments section.

中文翻译：

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细胞信号传导模型揭示了高危神经母细胞瘤的分子机制，并预测疾病的结果。

背景技术尽管神经母细胞瘤疗法取得了进展，但高危患者的死亡率仍然很高（40-50％），并且该疾病的分子基础仍然知之甚少。最近，使用数学模型来证明通过c-Jun N端激酶途径调节应激信号的网络在成神经细胞瘤患者的生存中起着至关重要的作用，而不论其MYCN扩增状态如何。这证明了用于发现疾病的潜在分子机制的生物模块计算模型的巨大潜力。结果由于已知信号与癌症高度相关，因此我们使用了整个细胞信号网络的计算模型来了解神经母细胞瘤预后不良的分子决定因素。我们的模型对神经母细胞瘤的发生和发展的分子机制产生了全面的了解。结论我们还显示了信号回路的活动如何被视为可靠的基于模型的预后生物标志物。审阅者本文由Tim Beissbarth，Xiaowenzhong和Joanna Polanska审阅。有关完整的评论，请转到“评论者的评论”部分。