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  3. Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression

Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression

  • Nat Cell Biol. 2021 Jan;23(1):87-98. doi: 10.1038/s41556-020-00613-6.
Sujun Chen # 1 2 3 4,  Guanghui Zhu # 1 2 5 6,  Yue Yang # 1,  Fubo Wang # 1,  Yu-Tian Xiao 1,  Na Zhang 7,  Xiaojie Bian 8,  Yasheng Zhu 1,  Yongwei Yu 1,  Fei Liu 9,  Keqin Dong 1,  Javier Mariscal 10,  Yin Liu 11,  Fraser Soares 2,  Helen Loo Yau 2 3,  Bo Zhang 12,  Weidong Chen 12,  Chao Wang 12,  Dai Chen 12,  Qinghua Guo 12,  Zhengfang Yi 7,  Mingyao Liu 7,  Michael Fraser 2,  Daniel D De Carvalho 2 3,  Paul C Boutros 3 13 14 15 16 17,  Dolores Di Vizio 10 18 19 20,  Zhou Jiang 21,  Theodorus van der Kwast 2,  Alejandro Berlin 2 22,  Song Wu 5 6,  Jianhua Wang 23,  Housheng Hansen He 24 25,  Shancheng Ren 26
Affiliations

Affiliations

  • 1 Department of Urology, Shanghai Changhai Hospital, Shanghai, P. R. China.
  • 2 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • 3 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • 4 Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • 5 Urology Institute of Shenzhen University, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen, P. R. China.
  • 6 Department of Urological Surgery, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, P. R. China.
  • 7 East China Normal University, Shanghai, P. R. China.
  • 8 Cancer Institute, Shanghai Urological Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, P. R. China.
  • 9 Department of Urology, Cancer Hospital, Chinese Academy of Medical Sciences, Shanghai, P. R. China.
  • 10 Department of Surgery, Division of Cancer Biology and Therapeutics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 11 Department of Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P. R. China.
  • 12 Novel Bioinformatics Co., Ltd, Shanghai, P. R. China.
  • 13 Department of Human Genetics, University of California Los Angeles, Los Angeles, CA, USA.
  • 14 Department of Urology, University of California Los Angeles, Los Angeles, CA, USA.
  • 15 Jonsson Comprehensive Cancer Centre, University of California Los Angeles, Los Angeles, USA.
  • 16 Institute for Precision Health, University of California Los Angeles, Los Angeles, CA, USA.
  • 17 Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
  • 18 Samuel Oschin Comprehensive Cancer Institute, Division of Cancer Biology and Therapeutics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 19 Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • 20 Department of Biomedical Sciences, Division of Cancer Biology and Therapeutics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 21 Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P. R. China.
  • 22 Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
  • 23 Cancer Institute, Shanghai Urological Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, P. R. China. jianhuaw2007@qq.com.
  • 24 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Hansenhe@uhnresearch.ca.
  • 25 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Hansenhe@uhnresearch.ca.
  • 26 Department of Urology, Shanghai Changhai Hospital, Shanghai, P. R. China. renshancheng@gmail.com.
  • # Contributed equally.
PMID: 33420488 DOI: 10.1038/s41556-020-00613-6
Abstract

Prostate Cancer shows remarkable clinical heterogeneity, which manifests in spatial and clonal genomic diversity. By contrast, the transcriptomic heterogeneity of prostate tumours is poorly understood. Here we have profiled the transcriptomes of 36,424 single cells from 13 prostate tumours and identified the epithelial cells underlying disease aggressiveness. The tumour microenvironment (TME) showed activation of multiple progression-associated transcriptomic programs. Notably, we observed promiscuous KLK3 expression and validated the ability of Cancer cells in altering T-cell transcriptomes. Profiling of a primary tumour and two matched lymph nodes provided evidence that KLK3 ectopic expression is associated with micrometastases. Close cell-cell communication exists among cells. We identified an endothelial subset harbouring active communication (activated endothelial cells, aECs) with tumour cells. Together with Sequencing of an additional 11 samples, we showed that aECs are enriched in castration-resistant prostate Cancer and promote Cancer cell invasion. Finally, we created a user-friendly web interface for users to explore the sequenced data.

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