Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity.
Nat Commun
; 9(1): 3917, 2018 09 25.
Article
em En
| MEDLINE
| ID: mdl-30254278
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Regulação Neoplásica da Expressão Gênica
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Proteína BRCA1
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Microambiente Tumoral
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article