The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells

Cancer Cell. 2020 Feb 10;37(2):226-242.e7. doi: 10.1016/j.ccell.2020.01.003.

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.

Keywords: fallopian tube; non-genetic heterogeneity; ovarian cancer; single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology
  • Epithelial Cells / pathology*
  • Epithelium / metabolism
  • Epithelium / pathology
  • Fallopian Tube Neoplasms / genetics
  • Fallopian Tube Neoplasms / metabolism*
  • Fallopian Tube Neoplasms / pathology
  • Fallopian Tubes / metabolism
  • Fallopian Tubes / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genetic Heterogeneity
  • Humans
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*