dc.contributor.author | Nawaz, S | |
dc.contributor.author | Trahearn, NA | |
dc.contributor.author | Heindl, A | |
dc.contributor.author | Banerjee, S | |
dc.contributor.author | Maley, CC | |
dc.contributor.author | Sottoriva, A | |
dc.contributor.author | Yuan, Y | |
dc.date.accessioned | 2020-05-28T12:04:11Z | |
dc.date.issued | 2019-10-21 | |
dc.identifier.citation | EBioMedicine, 2019, 48 pp. 224 - 235 | |
dc.identifier.issn | 2352-3964 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3657 | |
dc.identifier.eissn | 2352-3964 | |
dc.identifier.doi | 10.1016/j.ebiom.2019.10.001 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 224 - 235 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Ovarian Neoplasms | |
dc.subject | Disease Susceptibility | |
dc.subject | Diagnostic Imaging | |
dc.subject | Neoplasm Staging | |
dc.subject | Prognosis | |
dc.subject | Proportional Hazards Models | |
dc.subject | Mutation | |
dc.subject | Female | |
dc.subject | Kaplan-Meier Estimate | |
dc.title | Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-10-01 | |
rioxxterms.versionofrecord | 10.1016/j.ebiom.2019.10.001 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-10-21 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | EBioMedicine | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Computational Pathology & Integrated Genomics | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 48 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Computational Pathology & Integrated Genomics | |
dc.contributor.icrauthor | Nawaz, Sidra | |
dc.contributor.icrauthor | Sottoriva, Andrea | |
dc.contributor.icrauthor | Yuan, Yinyin | |