| Literature DB >> 32049047 |
Zhiyuan Hu1, Mara Artibani2, Abdulkhaliq Alsaadi3, Nina Wietek4, Matteo Morotti4, Tingyan Shi3, Zhe Zhong3, Laura Santana Gonzalez3, Salma El-Sahhar3, Mohammad KaramiNejadRanjbar3, Garry Mallett3, Yun Feng5, Kenta Masuda3, Yiyan Zheng3, Kay Chong3, Stephen Damato6, Sunanda Dhar6, Leticia Campo7, Riccardo Garruto Campanile8, Hooman Soleymani Majd8, Vikram Rai9, David Maldonado-Perez10, Stephanie Jones11, Vincenzo Cerundolo12, Tatjana Sauka-Spengler13, Christopher Yau14, Ahmed Ashour Ahmed15.
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.Entities:
Keywords: fallopian tube; non-genetic heterogeneity; ovarian cancer; single-cell RNA sequencing
Mesh：
Year: 2020 PMID： 32049047 DOI： 10.1016/j.ccell.2020.01.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743