Journal article
YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence
Oncotarget, Vol.6(10), pp.7470-7480
04/10/2015
DOI: 10.18632/oncotarget.3477
PMID: 25797255
Abstract
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.
Details
- Title: Subtitle
- YB-1 and MTA1 protein levels and not DNA or mRNA alterations predict for prostate cancer recurrence
- Creators
- Christine Moore Sheridan - University of California, San FranciscoTristan R. Grogan - University of California, Los AngelesHao G Nguyen - University of California, San FranciscoColette Galet - VA Greater Los Angeles Healthcare SystemMatthew B. Rettig - University of California, Los AngelesAndrew C. Hsieh - Fred Hutch Cancer CenterDavide Ruggero - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- Oncotarget, Vol.6(10), pp.7470-7480
- DOI
- 10.18632/oncotarget.3477
- PMID
- 25797255
- NLM abbreviation
- Oncotarget
- ISSN
- 1949-2553
- eISSN
- 1949-2553
- Publisher
- Impact Journals Llc
- Number of pages
- 11
- Grant note
- R01CA154916 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Goldberg-Benioff Program in Cancer Translational Biology UL1TR000124 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Language
- English
- Date published
- 04/10/2015
- Academic Unit
- Injury Prevention Research Center; University of Iowa Health Care
- Record Identifier
- 9985138030802771
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