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

被引：0
作者：
Tongtong Kan
Shupeng Zhang
Shengtao Zhou
Ya Zhang
Yun Zhao
Yinghua Gao
Tao Zhang
Feng Gao
Xin Wang
Linjie Zhao
Mengsu Yang
机构：
[1] City University of Hong Kong,Department of Biomedical Sciences
[2] Beijing Institute of Basic Medical Sciences,Department of Pathology
[3] The Second Affiliated Hospital of Shandong First Medical University,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 Labor
[4] West China Hospital,Department of Pathology
[5] Sichuan University,Department of Biostatistics, School of Public Health
[6] Taian Tumor Prevention and Treatment Hospital,Key Laboratory of Biochip Technology, Shenzhen Research Institute
[7] Shandong University,undefined
[8] City University of Hong Kong,undefined
来源：
Oncogene | 2022年 / 41卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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.
引用
收藏
页码：895 / 906
页数：11
相关论文
共 212 条
  • [11] Distefano MG(2011)Framework models of tumor dormancy from patient-derived observations Curr Opin Genet Dev 21 42-9
  • [12] Scambia G(2013)Microenvironmental regulation of tumor progression and metastasis Nat Med 19 1423-37
  • [13] Ferrandina G(2018)Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma EMBO J 37 e98772-74
  • [14] Hennessy BT(2011)Hallmarks of cancer: the next generation Cell 144 646-84
  • [15] Coleman RL(2019)New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer Nat Rev Mol Cell Biol 20 69-22
  • [16] Markman M(2014)TGF-beta in CAF-mediated tumor growth and metastasis Semin Cancer Biol 25 15-40
  • [17] Cannistra SA(2020)Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites Oncogene 39 4227-63
  • [18] McGuire WP(1958)On protein synthesis Symp Soc Exp Biol 12 138-24.e24
  • [19] Hoskins WJ(2017)Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer Cell 171 1611-96
  • [20] Brady MF(2016)Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq Science 352 189-73
12345678910