新方法揭示漿液性卵巢癌的非遺傳異質(zhì)性
2020-02-14
來(lái)源：小柯機(jī)器人
英國(guó)牛津大學(xué)Ahmed Ashour Ahmed和Christopher Yau團(tuán)隊(duì)合作，通過(guò)對(duì)正常輸卵管上皮細(xì)胞單細(xì)胞測(cè)序，發(fā)現(xiàn)了漿液性卵巢癌（SOC）的非遺傳異質(zhì)性（NGH）。相關(guān)論文2020年2月10日發(fā)表在《癌細(xì)胞》上。
研究人員發(fā)現(xiàn)，SOC中的NGH可以通過(guò)正常輸卵管上皮細(xì)胞（FTE）的分子標(biāo)記而得以準(zhǔn)確測(cè)定，這些細(xì)胞是 SOC的起源細(xì)胞。通過(guò)分析主要來(lái)自非卵巢癌患者的6,000個(gè)FTE細(xì)胞的轉(zhuǎn)錄組數(shù)據(jù)，研究人員確定了6個(gè)FTE亞型。 研究人員利用亞型特征來(lái)反卷積SOC表達(dá)數(shù)據(jù)，并發(fā)現(xiàn)大量腫瘤內(nèi)NGH。重要的是，約1,700個(gè)腫瘤的NGH分層與生存率密切相關(guān)。該研究為SOC的準(zhǔn)確預(yù)后和分期治療奠定了基礎(chǔ)。。
據(jù)了解，細(xì)胞狀態(tài)之間的相互改變促進(jìn)了癌細(xì)胞在壓力下的生存，并促進(jìn)了非遺傳異質(zhì)性（NGH）。 因此，NGH是腫瘤適應(yīng)力的替代指標(biāo)，但其定量結(jié)果卻受遺傳異質(zhì)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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