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pmid:26388710

Proteins from formalin-fixed paraffin-embedded prostate cancer sections that predict the risk of metastatic disease.

Jonathan C Dunne · David S Lamb · Brett Delahunt · Judith Murray · Peter Bethwaite · Peter Ferguson · John N Nacey · Sven Sondhauss · T William Jordan

Clinical proteomics · 2015 doi:10.1186/s12014-015-9096-3

Paper

complete

Experiment

complete

Data

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Analysis

partial

Execution

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Proteins from formalin-fixed paraffin-embedded prostate cancer sections that predict the risk of metastatic disease.
doi
10.1186/s12014-015-9096-3
pmid
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Jonathan C Dunne
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David S Lamb
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Brett Delahunt
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Judith Murray
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Peter Bethwaite
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Peter Ferguson
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John N Nacey
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Sven Sondhauss
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T William Jordan
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Clinical proteomics
year
2015
abstract
BACKGROUND: Prostate cancer is the most frequently diagnosed cancer in men and the third leading cause of cancer related deaths among men living in developed countries. Biomarkers that predict disease outcome at the time of initial diagnosis would substantially aid disease management. RESULTS: Proteins extracted from formalin-fixed paraffin-embedded tissue were identified using nanoflow liquid chromatography-MALDI MS/MS or after separation by one- or two-dimensional electrophoresis. The proteomics data have been deposited to the ProteomeXchange with identifier PXD000963. A list of potential biomarker candidates, based on proposed associations with prostate cancer, was derived from the 320 identified proteins. Candidate biomarkers were then examined by multiplexed Western blotting of archival specimens from men with premetastatic disease and subsequent disease outcome data. Annexin A2 provided the best prediction of risk of metastatic disease (log-rank Chi squared p = 0. 025). A tumor/control tissue >2-fold relative abundance increase predicted early biochemical failure, while <2-fold change predicted late or no biochemical failure. CONCLUSIONS: This study confirms the potential for use of archival FFPE specimens in the search for prognostic biomarkers for prostate cancer and suggests that annexin A2 abundance in diagnostic biopsies is predictive for metastatic potential. Protein profiling each cancer may lead to an overall reduction in mortality from metastatic prostate cancer as well as reduced treatment associated morbidity.
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The association of protein abundance measurements with time to biochemical failure was assessed in a univariate way using the Kaplan–Meier estimator for the survival function with cut-points chosen a priori while multivariate associations with biochemical failure were assessed by application of Cox proportional hazard modeling.
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Using multiplexed Western blotting of tumor and control regions from FFPE sections from 16 patients, followed by Kaplan–Meier and Cox proportional hazard analyses, ANXA2 abundance independently predicted biochemical-failure risk (Cox p = 0.018) and was the best predictor of metastatic-disease risk (log-rank p = 0.025).
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Proteins from formalin-fixed paraffin-embedded prostate cancer sections that predict the risk of metastatic disease
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Biomarkers that predict disease outcome at the time of initial diagnosis would substantially aid disease management.\nRESULTS: Proteins extracted from formalin-fixed paraffin-embedded tissue were identified using nanoflow liquid chromatography-MALDI MS/MS or after separation by one- or two-dimensional electrophoresis. The proteomics data have been deposited to the ProteomeXchange with identifier PXD000963. A list of potential biomarker candidates, based on proposed associations with prostate cancer, was derived from the 320 identified proteins. Candidate biomarkers were then examined by multiplexed Western blotting of archival specimens from men with premetastatic disease and subsequent disease outcome data. Annexin A2 provided the best prediction of risk of metastatic disease (log-rank Chi squared p = 0. 025). A tumor/control tissue >2-fold relative abundance increase predicted early biochemical failure, while <2-fold change predicted late or no biochemical failure.\nCONCLUSIONS: This study confirms the potential for use of archival FFPE specimens in the search for prognostic biomarkers for prostate cancer and suggests that annexin A2 abundance in diagnostic biopsies is predictive for metastatic potential. 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