Molecular subgroup of primary prostate cancer presenting with metastatic biology.
<h4>Background</h4> <p>Approximately 4–25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.</p> <h4>Objective</h4> <p>To identify a molecular subgroup of prostate cancers with metastatic potential at present...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Format: | Journal article |
Language: | English |
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Elsevier
2017
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_version_ | 1797087505006198784 |
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author | Walker, SM Knight, LA McCavigan, AM Logan, GE Berge, V Sherif, A Pandha, H Warren, AY Davidson, C Uprichard, A Blayney, JK Price, B Jellema, GL Steele, CJ Svindland, A McDade, SS Eden, CG Foster, C Mills, IG Neal, DE Mason, MD Kay, EW Waugh, DJ Harkin, DP Watson, RW Clarke, NW Kennedy, RD |
author_facet | Walker, SM Knight, LA McCavigan, AM Logan, GE Berge, V Sherif, A Pandha, H Warren, AY Davidson, C Uprichard, A Blayney, JK Price, B Jellema, GL Steele, CJ Svindland, A McDade, SS Eden, CG Foster, C Mills, IG Neal, DE Mason, MD Kay, EW Waugh, DJ Harkin, DP Watson, RW Clarke, NW Kennedy, RD |
author_sort | Walker, SM |
collection | OXFORD |
description | <h4>Background</h4> <p>Approximately 4–25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.</p> <h4>Objective</h4> <p>To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.</p> <h4>Design, setting, and participants</h4> <p>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.</p> <h4>Outcome measurements and statistical analysis</h4> <p>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.</p> <h4>Results and limitations</h4> <p>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</p> |
first_indexed | 2024-03-07T02:36:36Z |
format | Journal article |
id | oxford-uuid:a8ffec4f-3e79-4de9-b9c7-0b9ae3c89351 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T02:36:36Z |
publishDate | 2017 |
publisher | Elsevier |
record_format | dspace |
spelling | oxford-uuid:a8ffec4f-3e79-4de9-b9c7-0b9ae3c893512022-03-27T03:05:37ZMolecular subgroup of primary prostate cancer presenting with metastatic biology.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a8ffec4f-3e79-4de9-b9c7-0b9ae3c89351EnglishSymplectic Elements at OxfordElsevier2017Walker, SMKnight, LAMcCavigan, AMLogan, GEBerge, VSherif, APandha, HWarren, AYDavidson, CUprichard, ABlayney, JKPrice, BJellema, GLSteele, CJSvindland, AMcDade, SSEden, CGFoster, CMills, IGNeal, DEMason, MDKay, EWWaugh, DJHarkin, DPWatson, RWClarke, NWKennedy, RD <h4>Background</h4> <p>Approximately 4–25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.</p> <h4>Objective</h4> <p>To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.</p> <h4>Design, setting, and participants</h4> <p>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.</p> <h4>Outcome measurements and statistical analysis</h4> <p>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.</p> <h4>Results and limitations</h4> <p>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</p> |
spellingShingle | Walker, SM Knight, LA McCavigan, AM Logan, GE Berge, V Sherif, A Pandha, H Warren, AY Davidson, C Uprichard, A Blayney, JK Price, B Jellema, GL Steele, CJ Svindland, A McDade, SS Eden, CG Foster, C Mills, IG Neal, DE Mason, MD Kay, EW Waugh, DJ Harkin, DP Watson, RW Clarke, NW Kennedy, RD Molecular subgroup of primary prostate cancer presenting with metastatic biology. |
title | Molecular subgroup of primary prostate cancer presenting with metastatic biology. |
title_full | Molecular subgroup of primary prostate cancer presenting with metastatic biology. |
title_fullStr | Molecular subgroup of primary prostate cancer presenting with metastatic biology. |
title_full_unstemmed | Molecular subgroup of primary prostate cancer presenting with metastatic biology. |
title_short | Molecular subgroup of primary prostate cancer presenting with metastatic biology. |
title_sort | molecular subgroup of primary prostate cancer presenting with metastatic biology |
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