Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer
Background: Despite treatment advances, there remains a significant risk of recurrence in ovarian cancer, at which stage it is usually incurable. Consequently, there is a clear need for improved patient stratification. However, at present clinical prognosticators remain largely unchanged due to the...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419306644 |
| _version_ | 1811318368898121728 |
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| author | Sidra Nawaz Nicholas A. Trahearn Andreas Heindl Susana Banerjee Carlo C. Maley Andrea Sottoriva Yinyin Yuan |
| author_facet | Sidra Nawaz Nicholas A. Trahearn Andreas Heindl Susana Banerjee Carlo C. Maley Andrea Sottoriva Yinyin Yuan |
| author_sort | Sidra Nawaz |
| collection | DOAJ |
| description | Background: Despite treatment advances, there remains a significant risk of recurrence in ovarian cancer, at which stage it is usually incurable. Consequently, there is a clear need for improved patient stratification. However, at present clinical prognosticators remain largely unchanged due to the lack of reproducible methods to identify high-risk patients. Methods: In high-grade serous ovarian cancer patients with advanced disease, we spatially define a tumour ecological balance of stromal resource and immune hazard using high-throughput image and spatial analysis of routine histology slides. On this basis an EcoScore is developed to classify tumours by a shift in this balance towards cancer-favouring or inhibiting conditions. Findings: The EcoScore provides prognostic value stronger than, and independent of, known risk factors. Crucially, the clinical relevance of mutational burden and genomic instability differ under different stromal resource conditions, suggesting that the selective advantage of these cancer hallmarks is dependent on the context of stromal spatial structure. Under a high resource condition defined by a high level of geographical intermixing of cancer and stromal cells, selection appears to be driven by point mutations; whereas, in low resource tumours featured with high hypoxia and low cancer-immune co-localization, selection is fuelled by aneuploidy. Interpretation: Our study offers empirical evidence that cancer fitness depends on tumour spatial constraints, and presents a biological basis for developing better assessments of tumour adaptive strategies in overcoming ecological constraints including immune surveillance and hypoxia. Keywords: Tumour ecology, Tumour spatial heterogeneity, Cancer evolution, Ovarian cancer, Histological image analysis |
| first_indexed | 2024-04-13T12:24:18Z |
| format | Article |
| id | doaj.art-704d0afd473e4cad85d11af14f6cf40b |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-13T12:24:18Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-704d0afd473e4cad85d11af14f6cf40b2022-12-22T02:47:04ZengElsevierEBioMedicine2352-39642019-10-0148224235Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancerSidra Nawaz0Nicholas A. Trahearn1Andreas Heindl2Susana Banerjee3Carlo C. Maley4Andrea Sottoriva5Yinyin Yuan6Centre for Evolution and Cancer, Institute of Cancer Research, London, UK; Division of Molecular Pathology, Institute of Cancer Research, London, UKCentre for Evolution and Cancer, Institute of Cancer Research, London, UK; Division of Molecular Pathology, Institute of Cancer Research, London, UKCentre for Evolution and Cancer, Institute of Cancer Research, London, UK; Division of Molecular Pathology, Institute of Cancer Research, London, UKGynaecology Unit, Royal Marsden Hospital, London, UKCentre for Evolution and Cancer, Institute of Cancer Research, London, UK; Biodesign Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, USACentre for Evolution and Cancer, Institute of Cancer Research, London, UK; Division of Molecular Pathology, Institute of Cancer Research, London, UKCentre for Evolution and Cancer, Institute of Cancer Research, London, UK; Division of Molecular Pathology, Institute of Cancer Research, London, UK; Corresponding author: Dr Yinyin Yuan, Centre for Evolution and Cancer & Division of Molecular Pathology, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom.Background: Despite treatment advances, there remains a significant risk of recurrence in ovarian cancer, at which stage it is usually incurable. Consequently, there is a clear need for improved patient stratification. However, at present clinical prognosticators remain largely unchanged due to the lack of reproducible methods to identify high-risk patients. Methods: In high-grade serous ovarian cancer patients with advanced disease, we spatially define a tumour ecological balance of stromal resource and immune hazard using high-throughput image and spatial analysis of routine histology slides. On this basis an EcoScore is developed to classify tumours by a shift in this balance towards cancer-favouring or inhibiting conditions. Findings: The EcoScore provides prognostic value stronger than, and independent of, known risk factors. Crucially, the clinical relevance of mutational burden and genomic instability differ under different stromal resource conditions, suggesting that the selective advantage of these cancer hallmarks is dependent on the context of stromal spatial structure. Under a high resource condition defined by a high level of geographical intermixing of cancer and stromal cells, selection appears to be driven by point mutations; whereas, in low resource tumours featured with high hypoxia and low cancer-immune co-localization, selection is fuelled by aneuploidy. Interpretation: Our study offers empirical evidence that cancer fitness depends on tumour spatial constraints, and presents a biological basis for developing better assessments of tumour adaptive strategies in overcoming ecological constraints including immune surveillance and hypoxia. Keywords: Tumour ecology, Tumour spatial heterogeneity, Cancer evolution, Ovarian cancer, Histological image analysishttp://www.sciencedirect.com/science/article/pii/S2352396419306644 |
| spellingShingle | Sidra Nawaz Nicholas A. Trahearn Andreas Heindl Susana Banerjee Carlo C. Maley Andrea Sottoriva Yinyin Yuan Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer EBioMedicine |
| title | Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer |
| title_full | Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer |
| title_fullStr | Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer |
| title_full_unstemmed | Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer |
| title_short | Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer |
| title_sort | analysis of tumour ecological balance reveals resource dependent adaptive strategies of ovarian cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419306644 |
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