Department of Chemistry, Rice University, Houston, TX 77005-1892, United States of America.
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1892, United States of America.
Phys Biol. 2022 Aug 18;19(5). doi: 10.1088/1478-3975/ac8515.
It is widely believed that biological tissues evolved to lower the risks of cancer development. One of the specific ways to minimize the chances of tumor formation comes from proper spatial organization of tissues. However, the microscopic mechanisms of underlying processes remain not fully understood. We present a theoretical investigation on the role of spatial structures in cancer initiation dynamics. In our approach, the dynamics of single mutation fixations are analyzed using analytical calculations and computer simulations by mapping them to Moran processes on graphs with different connectivity that mimic various spatial structures. It is found that while the fixation probability is not affected by modifying the spatial structures of the tissues, the fixation times can change dramatically. The slowest dynamics is observed in 'quasi-one-dimensional' structures, while the fastest dynamics is observed in 'quasi-three-dimensional' structures. Theoretical calculations also suggest that there is a critical value of the degree of graph connectivity, which mimics the spatial dimension of the tissue structure, above which the spatial structure of the tissue has no effect on the mutation fixation dynamics. An effective discrete-state stochastic model of cancer initiation is utilized to explain our theoretical results and predictions. Our theoretical analysis clarifies some important aspects on the role of the tissue spatial structures in the cancer initiation processes.
人们普遍认为，生物组织的进化降低了癌症发展的风险。降低肿瘤形成几率的具体方法之一来自于组织的适当空间组织。然而，潜在过程的微观机制仍不完全清楚。我们提出了一种关于空间结构在癌症起始动力学中的作用的理论研究。在我们的方法中，通过将它们映射到模拟各种空间结构的具有不同连通性的图上的 Moran 过程，使用解析计算和计算机模拟来分析单个突变固定的动力学。结果发现，虽然固定概率不受改变组织的空间结构的影响，但固定时间可以发生剧烈变化。在“准一维”结构中观察到最慢的动力学，而在“准三维”结构中观察到最快的动力学。理论计算还表明，存在一个图连通度的临界值，它模拟了组织结构的空间维度，高于该值，组织的空间结构对突变固定动力学没有影响。利用有效的癌症起始离散状态随机模型来解释我们的理论结果和预测。我们的理论分析澄清了组织空间结构在癌症起始过程中的作用的一些重要方面。
