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

被引：34

作者：

Wang, Ziwei ^{[1
]}

Wang, Tao ^{[2
]}

Hong, Danni ^{[3
]}

Dong, Baijun ^{[4
]}

Wang, Yan ^{[1
]}

Huang, Huaqiang ^{[3
]}

Zhang, Wenhui ^{[1
]}

Lian, Bijun ^{[5
]}

Ji, Boyao ^{[6
]}

Shi, Haoqing ^{[1
]}

Qu, Min ^{[1
]}

Gao, Xu ^{[1
]}

Li, Daofeng ^{[7
]}

Collins, Colin ^{[8
]}

Wei, Gonghong ^{[9
]}

Xu, Chuanliang ^{[1
]}

Lee, Hyung Joo ^{[7
,10
]}

Huang, Jialiang ^{[3
,11
]}

Li, Jing ^{[12
,13
]}

机构：

[1] Naval Med Univ, Changhai Hosp, Dept Urol, Shanghai 200433, Peoples R China

[2] Zhengzhou Univ, Dept Urol, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China

[3] Xiamen Univ, Innovat Ctr Cell Signaling Network, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China

[4] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Urol, Shanghai 200127, Peoples R China

[5] 903rd PLA Hosp, Dept Urol, Hangzhou 310012, Zhejiang, Peoples R China

[6] Naval Med Univ, Dept Histol & Embryol, Shanghai 200433, Peoples R China

[7] Washington Univ, Sch Med, Dept Genet, Edison Family Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA

[8] Univ British Columbia, Dept Urol Sci, Vancouver, BC, Canada

[9] Fudan Univ, Shanghai Canc Ctr, Shanghai Med Coll, Dept Biochem & Mol Biol,Sch Basic Med Sci, Shanghai, Peoples R China

[10] Pin Pharmaceut, San Francisco, CA USA

[11] Xiamen Univ, Natl Inst Data Sci Hlth & Med, Xiamen 316005, Fujian, Peoples R China

[12] Naval Med Univ, Ctr Translat Med, Dept Bioinformat, Shanghai 200433, Peoples R China

[13] Shanghai Key Lab Cell Engn, Shanghai, Peoples R China

来源：

ISCIENCE | 2022年 / 25卷 / 07期

基金：

中国国家自然科学基金;

关键词：

DIFFERENTIATION; CARCINOMA; PROGRESSION; DISCOVERY; TUMORS;

D O I：

10.1016/j.isci.2022.104576

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-naive 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.

引用

页数：21

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