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YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence

Attempts to identify biomarkers to detect prostate tumorigenesis, and thus minimize prostate cancer progression and inform treatment decisions have primarily focused on alterations at the DNA and mRNA levels, ignoring alterations at the level of protein synthesis control. We have previously shown th...

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Autores principales: Sheridan, Christine Moore, Grogan, Tristan R., Nguyen, Hao G., Galet, Colette, Rettig, Matthew B., Hsieh, Andrew C., Ruggero, Davide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480693/
https://www.ncbi.nlm.nih.gov/pubmed/25797255
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author Sheridan, Christine Moore
Grogan, Tristan R.
Nguyen, Hao G.
Galet, Colette
Rettig, Matthew B.
Hsieh, Andrew C.
Ruggero, Davide
author_facet Sheridan, Christine Moore
Grogan, Tristan R.
Nguyen, Hao G.
Galet, Colette
Rettig, Matthew B.
Hsieh, Andrew C.
Ruggero, Davide
author_sort Sheridan, Christine Moore
collection PubMed
description Attempts to identify biomarkers to detect prostate tumorigenesis, and thus minimize prostate cancer progression and inform treatment decisions have primarily focused on alterations at the DNA and mRNA levels, ignoring alterations at the level of protein synthesis control. We have previously shown that the PI3K-AKT-mTOR pathway, frequently deregulated in prostate cancer, specifically induces the synthesis of proteins that contribute to metastasis, most notably YB-1 and MTA1, without altering mRNA levels thereby demonstrating the importance of translation control in driving the expression of these genes in cancer. Here, we analyze genomic sequencing and mRNA expression databases, as well as protein expression employing an annotated tissue microarray generated from 332 prostate cancer patients with 15 years of clinical follow-up to determine the combined prognostic capability of YB-1 and MTA1 alterations in forecasting prostate cancer outcomes. Remarkably, protein abundance, but not genomic or transcriptional alterations of YB-1 and MTA1, is predictive of disease recurrence, exhibiting a dose-dependent effect on time to PSA recurrence, an indicator of tumor relapse. Moreover, high protein levels of YB-1 and MTA1 are associated with a 3-fold increased risk for requiring future hormone therapy or radiation therapy. Importantly, YB-1 and MTA1 protein levels significantly increase the predictive capacity of a clinical model for prostate cancer recurrence. These findings demonstrate that protein abundance of YB-1 and MTA1, irrespective of DNA or mRNA status, can predict for prostate cancer relapse and uncover a vast underappreciated repository of biomarkers regulated at the level of protein expression.
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spelling pubmed-44806932015-06-26 YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence Sheridan, Christine Moore Grogan, Tristan R. Nguyen, Hao G. Galet, Colette Rettig, Matthew B. Hsieh, Andrew C. Ruggero, Davide Oncotarget Research Paper Attempts to identify biomarkers to detect prostate tumorigenesis, and thus minimize prostate cancer progression and inform treatment decisions have primarily focused on alterations at the DNA and mRNA levels, ignoring alterations at the level of protein synthesis control. We have previously shown that the PI3K-AKT-mTOR pathway, frequently deregulated in prostate cancer, specifically induces the synthesis of proteins that contribute to metastasis, most notably YB-1 and MTA1, without altering mRNA levels thereby demonstrating the importance of translation control in driving the expression of these genes in cancer. Here, we analyze genomic sequencing and mRNA expression databases, as well as protein expression employing an annotated tissue microarray generated from 332 prostate cancer patients with 15 years of clinical follow-up to determine the combined prognostic capability of YB-1 and MTA1 alterations in forecasting prostate cancer outcomes. Remarkably, protein abundance, but not genomic or transcriptional alterations of YB-1 and MTA1, is predictive of disease recurrence, exhibiting a dose-dependent effect on time to PSA recurrence, an indicator of tumor relapse. Moreover, high protein levels of YB-1 and MTA1 are associated with a 3-fold increased risk for requiring future hormone therapy or radiation therapy. Importantly, YB-1 and MTA1 protein levels significantly increase the predictive capacity of a clinical model for prostate cancer recurrence. These findings demonstrate that protein abundance of YB-1 and MTA1, irrespective of DNA or mRNA status, can predict for prostate cancer relapse and uncover a vast underappreciated repository of biomarkers regulated at the level of protein expression. Impact Journals LLC 2015-03-03 /pmc/articles/PMC4480693/ /pubmed/25797255 Text en Copyright: © 2015 Sheridan 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
Sheridan, Christine Moore
Grogan, Tristan R.
Nguyen, Hao G.
Galet, Colette
Rettig, Matthew B.
Hsieh, Andrew C.
Ruggero, Davide
YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence
title YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence
title_full YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence
title_fullStr YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence
title_full_unstemmed YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence
title_short YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence
title_sort yb-1 and mta1 protein levels and not dna or mrna alterations predict for prostate cancer recurrence
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480693/
https://www.ncbi.nlm.nih.gov/pubmed/25797255
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