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.

中文翻译：

---

正常输卵管上皮细胞的单细胞测序揭示了浆液性卵巢癌非遗传异质性。

细胞状态之间的相互分化促进癌细胞在压力下存活并促进非遗传异质性（NGH）。因此，NGH 是肿瘤恢复能力的替代指标，但其量化受到遗传异质性的影响。在这里，我们表明，当通过正常输卵管上皮 (FTE) 细胞（SOC 的起源细胞）的分子特征了解时，可以准确测量浆液性卵巢癌 (SOC) 中的 NGH。通过调查约 6,000 个 FTE 细胞（主要来自非卵巢癌患者）的转录组，确定了 6 种 FTE 亚型。我们使用亚型特征对 SOC 表达数据进行解卷积，发现了大量的肿瘤内 NGH。重要的是，基于 NGH 的约 1,700 个肿瘤的分层与生存率密切相关。我们的研究结果为 SOC 的准确预后和治疗分层奠定了基础。