新方法揭示浆液性卵巢癌的非遗传异质性
2020-02-14   阅读:363   来源:细胞

英国牛津大学Ahmed Ashour Ahmed和Christopher Yau团队合作,通过对正常输卵管上皮细胞单细胞测序,发现了浆液性卵巢癌(SOC)的非遗传异质性(NGH)。相关论文2020年2月10日发表在《癌细胞》上。

研究人员发现,SOC中的NGH可以通过正常输卵管上皮细胞(FTE)的分子标记而得以准确测定,这些细胞是 SOC的起源细胞。通过分析主要来自非卵巢癌患者的6,000个FTE细胞的转录组数据,研究人员确定了6个FTE亚型。 研究人员利用亚型特征来反卷积SOC表达数据,并发现大量肿瘤内NGH。重要的是,约1,700个肿瘤的NGH分层与生存率密切相关。该研究为SOC的准确预后和分期治疗奠定了基础。。

据了解,细胞状态之间的相互改变促进了癌细胞在压力下的生存,并促进了非遗传异质性(NGH)。 因此,NGH是肿瘤适应力的替代指标,但其定量结果却受遗传异质性的干扰。

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

编辑:小柯机器人

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