Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity.
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Date
2018-09-25Author
Heindl, A
Khan, AM
Rodrigues, DN
Eason, K
Sadanandam, A
Orbegoso, C
Punta, M
Sottoriva, A
Lise, S
Banerjee, S
Yuan, Y
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Lymphocytes
Stromal Cells
Humans
Ovarian Neoplasms
BRCA1 Protein
Prognosis
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Kaplan-Meier Estimate
Tumor Microenvironment
Cell Plasticity
Research team
Computational Pathology & Integrated Genomics
Systems and Precision Cancer Medicine
Language
eng
Date accepted
2018-08-15
License start date
2018-09-25
Citation
Nature communications, 2018, 9 (1), pp. 3917 - ?
Publisher
NATURE RESEARCH