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

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.

Automated summary

This study utilizes single-cell RNA sequencing to investigate the development and origin of relapse cells in epithelial ovarian cancers (EOCs). The researchers identified seven distinct subpopulations in primary tumors, with the CYR61(+) stress subpopulation being identified as the relapse-initiators. They also discovered a subpopulation of RGS5(+) cancer-associated fibroblasts (CAFs) that strongly support tumor metastasis. Furthermore, the combined expression scores of CYR61/RGS5 were found to be significantly correlated with the relapse-free-survival of EOC patients and can be used as predictors of EOC recurrence.