Beyond cancer genes: colorectal cancer as robust intrinsic states formed by molecular interactions.
Beyond cancer genes: colorectal cancer as robust intrinsic states formed by molecular interactions.
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超越癌症基因：结直肠癌是由分子相互作用形成的强大的内在状态
DOI：
10.1098/rsob.170169
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发表时间：
2017-11
期刊：
影响因子：
5.8
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Yuan R;Zhang S;Yu J;Huang Y;Lu D;Cheng R;Huang S;Ao P;Zheng S;Hood L;Zhu X
结直肠癌（CRC）具有复杂的病理特征，违背了当前生物医学研究中流行的线性相加推理。在追求这样的复杂性背后的机制的理解，我们构建了一个核心的CRC分子-细胞相互作用网络，并研究其非线性动力学性质。假设和建模方法以前已经开发并在各种癌症研究中进行了测试。网络动力学揭示了几个有吸引力的盆地对应于正常的肠道表型和强大的肿瘤亚型，确定其不同的分子特征的景观。将模型结果与浙江大学附属第二医院患者的基因表达谱进行比较，作为验证。数值“驱动”实验表明，CRC发病机制可能取决于参与胃肠道发育的途径和与间充质谱系分化相关的分子，如Stat 5、BMP、维甲酸信号通路、Runx和Hox转录家族。我们表明，免疫刺激和治疗的多方面反应，以及不同的致癌和转移途径，可以在这样的框架下直接理解和分析。
Colorectal cancer (CRC) has complex pathological features that defy the linear-additive reasoning prevailing in current biomedicine studies. In pursuing a mechanistic understanding behind such complexity, we constructed a core molecular–cellular interaction network underlying CRC and investigated its nonlinear dynamical properties. The hypothesis and modelling method has been developed previously and tested in various cancer studies. The network dynamics reveal a landscape of several attractive basins corresponding to both normal intestinal phenotype and robust tumour subtypes, identified by their different molecular signatures. Comparison between the modelling results and gene expression profiles from patients collected at the second affiliated hospital of Zhejiang University is presented as validation. The numerical ‘driving’ experiment suggests that CRC pathogenesis may depend on pathways involved in gastrointestinal track development and molecules associated with mesenchymal lineage differentiation, such as Stat5, BMP, retinoic acid signalling pathways, Runx and Hox transcription families. We show that the multi-faceted response to immune stimulation and therapies, as well as different carcinogenesis and metastasis routes, can be straightforwardly understood and analysed under such a framework.
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影响因子：
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作者：
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影响因子：
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