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

Sujun Chen^#^{1

2

3

4}, Guanghui Zhu^#^{1

2

5

6}, Yue Yang^#¹, Fubo Wang^#¹, Yu-Tian Xiao¹, Na Zhang⁷, Xiaojie Bian⁸, Yasheng Zhu¹, Yongwei Yu¹, Fei Liu⁹, Keqin Dong¹, Javier Mariscal¹⁰, Yin Liu¹¹, Fraser Soares², Helen Loo Yau^{2

3}, Bo Zhang¹², Weidong Chen¹², Chao Wang¹², Dai Chen¹², Qinghua Guo¹², Zhengfang Yi⁷, Mingyao Liu⁷, Michael Fraser², Daniel D De Carvalho^{2

3}, Paul C Boutros^{3

13

14

15

16

17}, Dolores Di Vizio^{10

18

19

20}, Zhou Jiang²¹, Theodorus van der Kwast², Alejandro Berlin^{2

22}, Song Wu^{5

6}, Jianhua Wang²³, Housheng Hansen He^{24

25}, Shancheng Ren²⁶

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

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

Sujun Chen et al. Nat Cell Biol. 2021 Jan.

. 2021 Jan;23(1):87-98.

doi: 10.1038/s41556-020-00613-6. Epub 2021 Jan 8.

Authors

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.

PubMed Disclaimer

Comment in

Prostate cancer hijacks the microenvironment.
Thienger P, Rubin MA. Thienger P, et al. Nat Cell Biol. 2021 Jan;23(1):3-5. doi: 10.1038/s41556-020-00616-3. Nat Cell Biol. 2021. PMID: 33420486 No abstract available.

References

1. Ferlay, J. et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer 144, 1941–1953 (2019). - PubMed - DOI
1. Weiner, A. B., Matulewicz, R. S., Eggener, S. E. & Schaeffer, E. M. Increasing incidence of metastatic prostate cancer in the United States (2004–2013). Prostate Cancer Prostatic Dis. 19, 395–397 (2016). - PubMed - DOI
1. Chen, S. et al. Widespread and functional RNA circularization in localized prostate cancer. Cell 176, 831–843 (2019). - PubMed - DOI
1. Cancer Genome Atlas Research Network The molecular taxonomy of primary prostate cancer. Cell 163, 1011–1025 (2015).
1. You, S. et al. Integrated classification of prostate cancer reveals a novel luminal subtype with poor outcome. Cancer Res. 76, 4948–4958 (2016). - PubMed - PMC - DOI

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Miscellaneous