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作者

Tongtong Kan Shupeng Zhang Shengtao Zhou Ya Zhang Yun Zhao Yinghua Gao Tao Zhang Feng Gao Xin Wang Linjie Zhao Mengsu Yang

作者单位

Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China Tongtong Kan, Feng Gao, Xin Wang & Mengsu Yang <<#>> Beijing Institute of Basic Medical Sciences, Beijing, China Tongtong Kan <<#>> Department of Pathology, The Second Affiliated Hospital of Shandong First Medical University, Taian, China Shupeng Zhang, Ya Zhang & Yinghua Gao <<#>> Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second Hospital and State Key Laboratory of Biotherapy/Collaborative Innovation Center, West China Hospital, Sichuan University, Chengdu, China Shengtao Zhou & Linjie Zhao <<#>> Department of Pathology, Taian Tumor Prevention and Treatment Hospital, Taian, China Yun Zhao <<#>> Department of Biostatistics, School of Public Health, Shandong University, Jinan, China Tao Zhang <<#>> Key Laboratory of Biochip Technology, Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China Mengsu Yang

刊名

Oncogene

年份

2022

卷号

Vol.41 No.6

页码

895-906

ISSN

0950-9232

关键词

GENE-EXPRESSION PROFILES STEM-CELLS HETEROGENEITY MECHANISMS GROWTH PROGRESSION RESISTANCE CYR61

摘要

Epithelial ovarian cancers 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 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...更多

Epithelial ovarian cancers 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 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 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.收起

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