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Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity

Author

Listed:
  • Andreas Heindl

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • Adnan Mujahid Khan

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • Daniel Nava Rodrigues

    (The Institute of Cancer Research)

  • Katherine Eason

    (The Institute of Cancer Research)

  • Anguraj Sadanandam

    (The Institute of Cancer Research
    Royal Marsden Hospital)

  • Cecilia Orbegoso

    (The Royal Marsden NHS Foundation Trust)

  • Marco Punta

    (The Institute of Cancer Research)

  • Andrea Sottoriva

    (The Institute of Cancer Research)

  • Stefano Lise

    (The Institute of Cancer Research)

  • Susana Banerjee

    (The Royal Marsden NHS Foundation Trust
    the Institute of Cancer Research)

  • Yinyin Yuan

    (The Institute of Cancer Research
    The Institute of Cancer Research)

Abstract

How tumor microenvironmental forces shape plasticity of cancer cell morphology is poorly understood. Here, we conduct automated histology image and spatial statistical analyses in 514 high grade serous ovarian samples to define cancer morphological diversification within the spatial context of the microenvironment. Tumor spatial zones, where cancer cell nuclei diversify in shape, are mapped in each tumor. Integration of this spatially explicit analysis with omics and clinical data reveals a relationship between morphological diversification and the dysregulation of DNA repair, loss of nuclear integrity, and increased disease mortality. Within the Immunoreactive subtype, spatial analysis further reveals significantly lower lymphocytic infiltration within diversified zones compared with other tumor zones, suggesting that even immune-hot tumors contain cells capable of immune escape. Our findings support a model whereby a subpopulation of morphologically plastic cancer cells with dysregulated DNA repair promotes ovarian cancer progression through positive selection by immune evasion.

Suggested Citation

  • Andreas Heindl & Adnan Mujahid Khan & Daniel Nava Rodrigues & Katherine Eason & Anguraj Sadanandam & Cecilia Orbegoso & Marco Punta & Andrea Sottoriva & Stefano Lise & Susana Banerjee & Yinyin Yuan, 2018. "Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06130-3
    DOI: 10.1038/s41467-018-06130-3
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    Cited by:

    1. Ting-Ting Gong & Shuang Guo & Fang-Hua Liu & Yun-Long Huo & Meng Zhang & Shi Yan & Han-Xiao Zhou & Xu Pan & Xin-Yue Wang & He-Li Xu & Ye Kang & Yi-Zi Li & Xue Qin & Qian Xiao & Dong-Hui Huang & Xiao-Y, 2023. "Proteomic characterization of epithelial ovarian cancer delineates molecular signatures and therapeutic targets in distinct histological subtypes," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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