期刊
CANCER CELL
卷 37, 期 2, 页码 226-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2020.01.003
关键词
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资金
- Ovarian Cancer Action and Oxford Biomedical Research Centre (BRC), National Institute for Health Research
- UK Medical Research Council [MR/L001411/1, MR/P02646X/1]
- Wellcome Trust [090532/Z/09/Z]
- Alan Turing Institute under EPSRC [EP/N510129/1]
- NIHR Oxford BRC
- NIHR Oxford BRC (Molecular Diagnostics Theme/Multimodal Pathology Subtheme)
- CRUK Oxford Centre
- EPSRC [EP/N510129/1] Funding Source: UKRI
- MRC [G0902418, MR/L001411/1, MR/P02646X/1, MR/P02646X/2] Funding Source: UKRI
The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of similar to 6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of similar to 1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.
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