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Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer.

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.

SUBMITTER: Nawaz S

PROVIDER: S-EPMC6838425 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer.

Nawaz Sidra S Trahearn Nicholas A NA Heindl Andreas A Banerjee Susana S Maley Carlo C CC Sottoriva Andrea A Yuan Yinyin Y

EBioMedicine 20191021

<h4>Background</h4>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.<h4>Methods</h4>In high-grade serous ovarian cancer patients with advanced disease, we spatially define a tumour ecological balance o ...[more]

PMID: 31648981

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Project description:Background and aims:The CSR classification categorizes plants as stress tolerators (S), ruderals (R) and competitors (C). Initially proposed as a general framework to describe ecological strategies across species, this scheme has recently been used to investigate the variation of strategies within species. For instance, ample variation along the S-R axis was found in Arabidopsis thaliana, with stress-tolerator accessions predominating in hot and dry regions, which was interpreted as a sign of functional adaptation to climate within the species. Methods:In this study the range of CSR strategies within A. thaliana was evaluated across 426 accessions originating from North Africa to Scandinavia. A position in the CSR strategy space was allocated for every accession based on three functional traits: leaf area, leaf dry matter content (LDMC) and specific leaf area (SLA). Results were related to climate at origin and compared with a previous study performed on the same species. Furthermore, the role of natural selection in phenotypic differentiation between lineages was investigated with QST-FST comparisons, using the large amount of genetic information available for this species. Key Results:Substantial variation in ecological strategies along the S-R axis was found in A. thaliana. By contrast with previous findings, stress-tolerator accessions predominated in cold climates, notably Scandinavia, where late flowering was associated with traits related to resource conservation, such as high LDMC and low SLA. Because of trait plasticity, variations in CSR classification in relation to growth conditions were also observed for the same genotypes. Conclusions:There is a latitudinal gradient of ecological strategies in A. thaliana as a result of within-species adaptation to climate. Our study also underlines the importance of growth conditions and of the methodology used for trait measurement, notably age versus stage measurement, to infer the strength and direction of trait-environment relationships. This highlights the potential and limitations of the CSR classification in explaining functional adaptation to the environment.

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Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer.

Publications

Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer.

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