Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer
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. F...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222008483 |
| _version_ | 1811334262746513408 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ziwei Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T17:05:11Z |
| format | Article |
| id | doaj.art-778135850e694ffdb49f9147fdaee4c0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T17:05:11Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-778135850e694ffdb49f9147fdaee4c02022-12-22T02:38:30ZengElsevieriScience2589-00422022-07-01257104576Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancerZiwei Wang0Tao Wang1Danni Hong2Baijun Dong3Yan Wang4Huaqiang Huang5Wenhui Zhang6Bijun Lian7Boyao Ji8Haoqing Shi9Min Qu10Xu Gao11Daofeng Li12Colin Collins13Gonghong Wei14Chuanliang Xu15Hyung Joo Lee16Jialiang Huang17Jing Li18Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaDepartment of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaDepartment of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaDepartment of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaDepartment of Urology, the 903rd PLA Hospital, Hangzhou, Zhejiang 310012, ChinaDepartment of Histology and Embryology, Naval Medical University, Shanghai 200433, ChinaDepartment of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaDepartment of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaDepartment of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, ChinaDepartment of Genetics, Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USADepartment of Urologic Sciences, University of British Columbia, CanadaFudan University Shanghai Cancer Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, ChinaDepartment of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; Corresponding authorDepartment 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 authorState 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 authorDepartment of Bioinformatics, Center for Translational Medicine, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory of Cell Engineering, Shanghai, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222008483Cancer systems biologyCancerTranscriptomics |
| spellingShingle | 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 Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer iScience Cancer systems biology Cancer Transcriptomics |
| title | Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer |
| title_full | Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer |
| title_fullStr | Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer |
| title_full_unstemmed | Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer |
| title_short | Single-cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer |
| title_sort | single cell transcriptional regulation and genetic evolution of neuroendocrine prostate cancer |
| topic | Cancer systems biology Cancer Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222008483 |
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