Malekian Negin, Habibi Jafar, Zangooei Mohammad Hossein, Aghakhani Hojjat
Software Engineering, Department of Computer Engineering, Sharif University of Technology, Azadi Avenue, Tehran, Iran.
Software Engineering, Department of Computer Engineering, Sharif University of Technology, Azadi Avenue, Tehran, Iran.
Comput Methods Programs Biomed. 2016 Nov;136:107-17. doi: 10.1016/j.cmpb.2016.08.011. Epub 2016 Aug 24.
There are many cells with various phenotypic behaviors in cancer interacting with each other. For example, an apoptotic cell may induce apoptosis in adjacent cells. A living cell can also protect cells from undergoing apoptosis and necrosis. These survival and death signals are propagated through interaction pathways between adjacent cells called gap junctions. The function of these signals depends on the cellular context of the cell receiving them. For instance, a receiver cell experiencing a low level of oxygen may interpret a received survival signal as an apoptosis signal. In this study, we examine the effect of these signals on tumor growth.
We make an evolutionary game theory component in order to model the signal propagation through gap junctions. The game payoffs are defined as a function of cellular context. Then, the game theory component is integrated into an agent-based model of tumor growth. After that, the integrated model is applied to ductal carcinoma in situ, a type of early stage breast cancer. Different scenarios are explored to observe the impact of the gap junction communication and parameters of the game theory component on cancer progression. We compare these scenarios by using the Wilcoxon signed-rank test.
The Wilcoxon signed-rank test succeeds in proving a significant difference between the tumor growth of the model before and after considering the gap junction communication. The Wilcoxon signed-rank test also proves that the tumor growth significantly depends on the oxygen threshold of turning survival signals into apoptosis.
In this study, the gap junction communication is modeled by using evolutionary game theory to illustrate its role at early stage cancers such as ductal carcinoma in situ. This work indicates that the gap junction communication and the oxygen threshold of turning survival signals into apoptosis can notably affect cancer progression.
癌症中有许多具有不同表型行为的细胞相互作用。例如，一个凋亡细胞可能诱导相邻细胞凋亡。一个活细胞也可以保护细胞免于凋亡和坏死。这些存活和死亡信号通过称为缝隙连接的相邻细胞间的相互作用途径进行传播。这些信号的功能取决于接收它们的细胞的细胞环境。例如，一个处于低氧水平的接收细胞可能将接收到的存活信号解读为凋亡信号。在本研究中，我们研究这些信号对肿瘤生长的影响。
我们构建了一个进化博弈论组件，以便对通过缝隙连接的信号传播进行建模。博弈收益被定义为细胞环境的函数。然后，将博弈论组件集成到一个基于主体的肿瘤生长模型中。之后，将集成模型应用于原位导管癌，一种早期乳腺癌。探索不同的情景以观察缝隙连接通讯和博弈论组件的参数对癌症进展的影响。我们使用Wilcoxon符号秩检验对这些情景进行比较。
Wilcoxon符号秩检验成功证明了在考虑缝隙连接通讯前后模型的肿瘤生长之间存在显著差异。Wilcoxon符号秩检验还证明肿瘤生长显著取决于将存活信号转变为凋亡信号的氧阈值。
在本研究中，通过使用进化博弈论对缝隙连接通讯进行建模，以阐明其在原位导管癌等早期癌症中的作用。这项工作表明，缝隙连接通讯以及将存活信号转变为凋亡信号的氧阈值可显著影响癌症进展。
