Spatial organization and correlations of cell nuclei in brain tumors

Yang Jiao, Hal Berman, Tim Rasmus Kiehl, Salvatore Torquato

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere27323
JournalPLoS One
Volume6
Issue number11
DOIs
StatePublished - Nov 16 2011
Externally publishedYes

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cell nucleus
Cell Nucleus
Brain Neoplasms
Tumors
Brain
Cells
brain
neoplasms
cells
Spatial distribution
Glioma
Statistics
Neoplasms
group behavior
Normal Distribution
statistics
Cell Count
spatial distribution

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Spatial organization and correlations of cell nuclei in brain tumors. / Jiao, Yang; Berman, Hal; Kiehl, Tim Rasmus; Torquato, Salvatore.

In: PLoS One, Vol. 6, No. 11, e27323, 16.11.2011.

Research output: Contribution to journalArticle

Jiao, Yang ; Berman, Hal ; Kiehl, Tim Rasmus ; Torquato, Salvatore. / Spatial organization and correlations of cell nuclei in brain tumors. In: PLoS One. 2011 ; Vol. 6, No. 11.
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