ArticleEBioMedicine2019
Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers.International journal of molecular sciences · 2023Review
- B-cells and regulatory T-cells in the microenvironment of HER2+ breast cancer are associated with decreased survival: a real-world analysis of women with HER2+ metastatic breast cancer.Breast cancer research : BCR · 2023Article
- Effective dose window for containing tumor burden under tolerable level.NPJ systems biology and applications · 2023Article
- The impact of the spatial heterogeneity of resistant cells and fibroblasts on treatment response.PLoS computational biology · 2022Article
- Digital Pathology-based Study of Cell- and Tissue-level Morphologic Features in Serous Borderline Ovarian Tumor and High-grade Serous Ovarian Cancer.Journal of pathology informatics · 2021Article
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Authors and funding
7 authors.
Funding
Abstract
backgroundDespite 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.
methodsIn 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.
findingsThe 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.
interpretationOur 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.
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