1. The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells.
- Author
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Hu Z, Artibani M, Alsaadi A, Wietek N, Morotti M, Shi T, Zhong Z, Santana Gonzalez L, El-Sahhar S, Carrami EM, Mallett G, Feng Y, Masuda K, Zheng Y, Chong K, Damato S, Dhar S, Campo L, Garruto Campanile R, Soleymani Majd H, Rai V, Maldonado-Perez D, Jones S, Cerundolo V, Sauka-Spengler T, Yau C, and Ahmed AA
- Subjects
- Cystadenocarcinoma, Serous genetics, Cystadenocarcinoma, Serous metabolism, Cystadenocarcinoma, Serous pathology, Epithelium metabolism, Epithelium pathology, Fallopian Tube Neoplasms genetics, Fallopian Tube Neoplasms pathology, Fallopian Tubes metabolism, Female, Gene Expression Regulation, Neoplastic genetics, Genetic Heterogeneity, Humans, Ovarian Neoplasms metabolism, Epithelial Cells pathology, Fallopian Tube Neoplasms metabolism, Fallopian Tubes pathology, Ovarian Neoplasms pathology
- Abstract
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 ∼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 ∼1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC., Competing Interests: Declaration of Interests A.A.A., C.Y., and Z.H. filed a patent application for the use of the 52-gene panel for predicting the prognosis in ovarian cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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