新方法揭示漿液性卵巢癌的非遺傳異質性
英國牛津大學Ahmed Ashour Ahmed和Christopher Yau團隊合作，通過對正常輸卵管上皮細胞單細胞測序，發(fā)現(xiàn)了漿液性卵巢癌（SOC）的非遺傳異質性（NGH）。相關論文2020年2月10日發(fā)表在《癌細胞》上。
研究人員發(fā)現(xiàn)，SOC中的NGH可以通過正常輸卵管上皮細胞（FTE）的分子標記而得以準確測定，這些細胞是 SOC的起源細胞。通過分析主要來自非卵巢癌患者的6,000個FTE細胞的轉錄組數(shù)據(jù)，研究人員確定了6個FTE亞型。 研究人員利用亞型特征來反卷積SOC表達數(shù)據(jù)，并發(fā)現(xiàn)大量腫瘤內NGH。重要的是，約1,700個腫瘤的NGH分層與生存率密切相關。該研究為SOC的準確預后和分期治療奠定了基礎。。
據(jù)了解，細胞狀態(tài)之間的相互改變促進了癌細胞在壓力下的生存，并促進了非遺傳異質性（NGH）。 因此，NGH是腫瘤適應力的替代指標，但其定量結果卻受遺傳異質性的干擾。
附：英文原文
Title: The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells
Author: Zhiyuan Hu, Mara Artibani, Abdulkhaliq Alsaadi, Nina Wietek, Matteo Morotti, Tingyan Shi, Zhe Zhong, Laura Santana Gonzalez, Salma El-Sahhar, Mohammad KaramiNejadRanjbar, Garry Mallett, Yun Feng, Kenta Masuda, Yiyan Zheng, Kay Chong, Stephen Damato, Sunanda Dhar, Leticia Campo, Riccardo Garruto Campanile, Hooman Soleymani majd, Vikram Rai, David Maldonado-Perez, Stephanie Jones, Vincenzo Cerundolo, Tatjana Sauka-Spengler, Christopher Yau, Ahmed Ashour Ahmed
Issue&Volume: 2020/02/10
Abstract: The inter-differentiation between cell states promotes cancer cell survival understress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogateof tumor resilience but its quantification is confounded by genetic heterogeneity.Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured wheninformed 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 usedsubtype signatures to deconvolute SOC expression data and found substantial intra-tumorNGH. Importantly, NGH-based stratification of ～1,700 tumors robustly correlated withsurvival. Our findings lay the foundation for accurate prognostic and therapeuticstratification of SOC.
DOI: 10.1016/j.ccell.2020.01.003
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30042-8
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