Journal article
Molecular subgroup of primary prostate cancer presenting with metastatic biology.
- Abstract:
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Background
Approximately 4–25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.
Objective
To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.
Design, setting, and participants
Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 [34TD DIF]months.
Outcome measurements and statistical analysis
Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis.
Results and limitations
A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay[35TD DIF] positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13–2.33]; p = 0.0092) and metastatic recurrence (multivariable HR = 3.20 [1.76–5.80]; p = 0.0001). A combined model with Cancer of the Prostate Risk Assessment [36TD DIF]post surgical (CAPRA-S) identified patients at an increased
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.3MB, Terms of use)
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- Publisher copy:
- 10.1016/j.eururo.2017.03.027
Authors
- Publisher:
- Elsevier
- Journal:
- European Urology More from this journal
- Volume:
- 72
- Issue:
- 4
- Pages:
- 509-518
- Publication date:
- 2017-04-01
- Acceptance date:
- 2017-03-17
- DOI:
- EISSN:
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1873-7560
- ISSN:
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0302-2838
- Pmid:
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28408174
- Language:
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English
- Keywords:
- Pubs id:
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pubs:690266
- UUID:
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uuid:a8ffec4f-3e79-4de9-b9c7-0b9ae3c89351
- Local pid:
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pubs:690266
- Source identifiers:
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690266
- Deposit date:
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2018-01-11
- ARK identifier:
Terms of use
- Copyright holder:
- European Association of Urology
- Copyright date:
- 2017
- Notes:
- © 2017 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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