Spatial Organization and Correlations of Cell Nuclei in Brain Tumors
Spatial Organization and Correlations of Cell Nuclei in Brain Tumors
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DOI：
10.1371/journal.pone.0027323
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发表时间：
2011-11-16
期刊：
影响因子：
3.7
通讯作者：
Torquato, Salvatore
中科院分区：
文献类型：
--
作者：
Jiao, Yang;Berman, Hal;Torquato, Salvatore
接受癌症是自组织、机会主义系统的假设，了解癌细胞在肿瘤异质环境中的集体行为至关重要。在本文中，我们提出以下基本问题：肿瘤进化的这种自组织是否反映在恶性细胞在异质环境中的空间分布方式上？我们采用异质介质理论中出现的各种重要的统计微观结构描述符来表征从组织学图像中获得的良性脑白质细胞和脑胶质瘤细胞的细胞核的空间分布。这些描述符包括对相关函数、结构因子和各种最近邻函数，以各种方式量化细胞核对在空间中的相关性。我们将细胞核的质心映射到点分布中，以表明虽然常用的局部空间统计（例如细胞面积和相邻细胞的数量）无法清楚地区分正常和异常细胞核分布的空间相关性，但上述微观结构描述符很好地捕获了它们显着的结构特征。我们发现肿瘤细胞比正常细胞更密集，并且在任何一对细胞之间表现出更强的有效排斥力。此外，我们证明脑胶质瘤是以集体方式组织的，而不是在中等和大长度尺度上随机组织的。异常细胞之间存在的重要空间相关性有力地支持了这样的观点：癌症不是恶性细胞的无组织集合，而是一个复杂的新兴集成系统。
Accepting the hypothesis that cancers are self-organizing, opportunistic systems, it is crucial to understand the collective behavior of cancer cells in their tumorous heterogeneous environment. In the present paper, we ask the following basic question: Is this self-organization of tumor evolution reflected in the manner in which malignant cells are spatially distributed in their heterogeneous environment? We employ a variety of nontrivial statistical microstructural descriptors that arise in the theory of heterogeneous media to characterize the spatial distributions of the nuclei of both benign brain white matter cells and brain glioma cells as obtained from histological images. These descriptors, which include the pair correlation function, structure factor and various nearest neighbor functions, quantify how pairs of cell nuclei are correlated in space in various ways. We map the centroids of the cell nuclei into point distributions to show that while commonly used local spatial statistics (e. g., cell areas and number of neighboring cells) cannot clearly distinguish spatial correlations in distributions of normal and abnormal cell nuclei, their salient structural features are captured very well by the aforementioned microstructural descriptors. We show that the tumorous cells pack more densely than normal cells and exhibit stronger effective repulsions between any pair of cells. Moreover, we demonstrate that brain gliomas are organized in a collective way rather than randomly on intermediate and large length scales. The existence of nontrivial spatial correlations between the abnormal cells strongly supports the view that cancer is not an unorganized collection of malignant cells but rather a complex emergent integrated system.