Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer

Ziwei Wang; Tao Wang; Danni Hong; Baijun Dong; Yan Wang; Huaqiang Huang; Wenhui Zhang; Bijun Lian; Boyao Ji; Haoqing Shi; Min Qu; Xu Gao; Daofeng Li; Colin Collins; Gonghong Wei; Chuanliang Xu; Hyung Joo Lee; Jialiang Huang; Jing Li

iScience (Jul 2022)

Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer

Ziwei Wang,
Tao Wang,
Danni Hong,
Baijun Dong,
Yan Wang,
Huaqiang Huang,
Wenhui Zhang,
Bijun Lian,
Boyao Ji,
Haoqing Shi,
Min Qu,
Xu Gao,
Daofeng Li,
Colin Collins,
Gonghong Wei,
Chuanliang Xu,
Hyung Joo Lee,
Jialiang Huang,
Jing Li

Affiliations

Ziwei Wang: Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Tao Wang: Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
Danni Hong: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China
Baijun Dong: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Yan Wang: Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Huaqiang Huang: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China
Wenhui Zhang: Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Bijun Lian: Department of Urology, the 903rd PLA Hospital, Hangzhou, Zhejiang 310012, China
Boyao Ji: Department of Histology and Embryology, Naval Medical University, Shanghai 200433, China
Haoqing Shi: Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Min Qu: Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Xu Gao: Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
Daofeng Li: Department of Genetics, Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
Colin Collins: Department of Urologic Sciences, University of British Columbia, Canada
Gonghong Wei: Fudan University Shanghai Cancer Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China
Chuanliang Xu: Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; Corresponding author
Hyung Joo Lee: Department of Genetics, Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA; Pin Pharmaceuticals, South San Francisco, CA, USA; Corresponding author
Jialiang Huang: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, Fujian 316005, China; Corresponding author
Jing Li: Department of Bioinformatics, Center for Translational Medicine, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory of Cell Engineering, Shanghai, China; Corresponding author

Journal volume & issue: Vol. 25, no. 7
p. 104576

Abstract

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Summary: Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer, with a 10% five-year survival rate. However, little is known about its origin and the mechanisms governing its emergence. Our study characterized ADPC and NEPC in prostate tumors from 7 patients using scRNA-seq. First, we identified two NEPC gene expression signatures representing different phases of trans-differentiation. New marker genes we identified may be used for clinical diagnosis. Second, integrative analyses combining expression and subclonal architecture revealed different paths by which NEPC diverges from the original ADPC, either directly from treatment-naïve tumor cells or from specific intermediate states of treatment-resistance. Third, we inferred a hierarchical transcription factor (TF) network underlying the progression, which involves constitutive regulation by ASCL1, FOXA2, and selective regulation by NKX2-2, POU3F2, and SOX2. Together, these results defined the complex expression profiles and advanced our understanding of the genetic and transcriptomic mechanisms leading to NEPC differentiation.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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