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Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect
PURPOSE: We evaluated gene expression in histologically normal-appearing tissue (NT) adjacent to prostate tumor in radical prostatectomy specimens, assessing for biological significance based on prediction of clinical recurrence (cR - metastatic disease or local recurrence). RESULTS: A total of 410...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085124/ https://www.ncbi.nlm.nih.gov/pubmed/27121323 http://dx.doi.org/10.18632/oncotarget.8944 |
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author | Magi-Galluzzi, Cristina Maddala, Tara Falzarano, Sara Moscovita Cherbavaz, Diana B. Zhang, Nan Knezevic, Dejan Febbo, Phillip G. Lee, Mark Lawrence, Hugh Jeffrey Klein, Eric A. |
author_facet | Magi-Galluzzi, Cristina Maddala, Tara Falzarano, Sara Moscovita Cherbavaz, Diana B. Zhang, Nan Knezevic, Dejan Febbo, Phillip G. Lee, Mark Lawrence, Hugh Jeffrey Klein, Eric A. |
author_sort | Magi-Galluzzi, Cristina |
collection | PubMed |
description | PURPOSE: We evaluated gene expression in histologically normal-appearing tissue (NT) adjacent to prostate tumor in radical prostatectomy specimens, assessing for biological significance based on prediction of clinical recurrence (cR - metastatic disease or local recurrence). RESULTS: A total of 410 evaluable patients had paired tumor and NT. Fortysix genes, representing diverse biological pathways (androgen signaling, stromal response, stress response, cellular organization, proliferation, cell adhesion, and chromatin remodeling) were associated with cR in NT (FDR < 20%), of which 39 concordantly predicted cR in tumor (FDR < 20%). Overall GPS and its stromal response and androgen-signaling gene group components also significantly predicted time to cR in NT (RM-corrected HR/20 units = 1.25; 95% CI: 1.01-1.56; P = 0.024). EXPERIMENTAL DESIGN: Expression of 732 genes was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) separately in tumor and adjacent NT specimens from 127 patients with and 374 without cR following radical prostatectomy for T1/T2 prostate cancer. A 17-gene expression signature (Genomic Prostate Score [GPS]), previously validated to predict aggressive prostate cancer when measured in tumor tissue, was also assessed using pre-specified genes and algorithms. Analysis used Cox proportional hazards models, Storey's false discovery rate (FDR) control, and regression to the mean (RM) correction. CONCLUSIONS: Gene expression profiles, including GPS, from NT adjacent to tumor can predict prostate cancer outcome. These findings suggest that there is a biologically significant field effect in primary prostate cancer that is a marker for aggressive disease. |
format | Online Article Text |
id | pubmed-5085124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50851242016-10-31 Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect Magi-Galluzzi, Cristina Maddala, Tara Falzarano, Sara Moscovita Cherbavaz, Diana B. Zhang, Nan Knezevic, Dejan Febbo, Phillip G. Lee, Mark Lawrence, Hugh Jeffrey Klein, Eric A. Oncotarget Research Paper PURPOSE: We evaluated gene expression in histologically normal-appearing tissue (NT) adjacent to prostate tumor in radical prostatectomy specimens, assessing for biological significance based on prediction of clinical recurrence (cR - metastatic disease or local recurrence). RESULTS: A total of 410 evaluable patients had paired tumor and NT. Fortysix genes, representing diverse biological pathways (androgen signaling, stromal response, stress response, cellular organization, proliferation, cell adhesion, and chromatin remodeling) were associated with cR in NT (FDR < 20%), of which 39 concordantly predicted cR in tumor (FDR < 20%). Overall GPS and its stromal response and androgen-signaling gene group components also significantly predicted time to cR in NT (RM-corrected HR/20 units = 1.25; 95% CI: 1.01-1.56; P = 0.024). EXPERIMENTAL DESIGN: Expression of 732 genes was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) separately in tumor and adjacent NT specimens from 127 patients with and 374 without cR following radical prostatectomy for T1/T2 prostate cancer. A 17-gene expression signature (Genomic Prostate Score [GPS]), previously validated to predict aggressive prostate cancer when measured in tumor tissue, was also assessed using pre-specified genes and algorithms. Analysis used Cox proportional hazards models, Storey's false discovery rate (FDR) control, and regression to the mean (RM) correction. CONCLUSIONS: Gene expression profiles, including GPS, from NT adjacent to tumor can predict prostate cancer outcome. These findings suggest that there is a biologically significant field effect in primary prostate cancer that is a marker for aggressive disease. Impact Journals LLC 2016-04-22 /pmc/articles/PMC5085124/ /pubmed/27121323 http://dx.doi.org/10.18632/oncotarget.8944 Text en Copyright: © 2016 Magi-Galluzzi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Magi-Galluzzi, Cristina Maddala, Tara Falzarano, Sara Moscovita Cherbavaz, Diana B. Zhang, Nan Knezevic, Dejan Febbo, Phillip G. Lee, Mark Lawrence, Hugh Jeffrey Klein, Eric A. Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect |
title | Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect |
title_full | Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect |
title_fullStr | Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect |
title_full_unstemmed | Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect |
title_short | Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect |
title_sort | gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085124/ https://www.ncbi.nlm.nih.gov/pubmed/27121323 http://dx.doi.org/10.18632/oncotarget.8944 |
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