Single-cell RNA-seq recognized the initiator of epithelial ovarian cancer recurrence

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Shupeng Zhang
  • Shengtao Zhou
  • Ya Zhang
  • Yun Zhao
  • Yinghua Gao
  • Tao Zhang
  • Linjie Zhao

Detail(s)

Original languageEnglish
Pages (from-to)895-906
Journal / PublicationOncogene
Volume41
Issue number6
Online published7 Jan 2022
Publication statusPublished - 4 Feb 2022

Abstract

Epithelial ovarian cancers (EOCs) are sensitive to chemotherapy but will ultimately relapse and develop drug resistance. The origin of EOC recurrence has been elusive due to intra-tumor heterogeneity. Here we performed single-cell RNA sequencing (scRNA-seq) in 13,369 cells from primary, untreated peritoneal metastasis, and relapse tumors. We used time-resolved analysis to chart the developmental sequence of cells from the metastatic tumors, then traced the earliest replanting cells back to the primary tumors. We discovered seven distinct subpopulations in primary tumors where the CYR61+ “stress” subpopulation was identified as the relapse-initiators. Furthermore, a subpopulation of RGS5+ cancer-associated fibroblasts (CAFs) was found to strongly support tumor metastasis. The combined CYR61/RGS5 expression scores significantly correlated with the relapse-free-survival of EOC patients and can be used as predictors of EOC recurrence. Our study provides insights into the mechanism of EOC recurrence and presents CYR61+ relapse-initiating cells as potential therapeutic targets to prevent EOC relapse.

Citation Format(s)

Single-cell RNA-seq recognized the initiator of epithelial ovarian cancer recurrence. / Kan, Tongtong; Zhang, Shupeng; Zhou, Shengtao; Zhang, Ya; Zhao, Yun; Gao, Yinghua; Zhang, Tao; Gao, Feng; Wang, Xin; Zhao, Linjie; Yang, Mengsu.

In: Oncogene, Vol. 41, No. 6, 04.02.2022, p. 895-906.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review