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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
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Experiment
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Data
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Analysis
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Complete file
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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. Protein profiling each cancer may lead to an overall reduction in mortality from metastatic prostate cancer as well as reduced treatment associated morbidity.", "claims": [{"id": "claim-method", "statement": "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.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26388710", "locator": "sections[10] \"Statistical methods\" paragraph 2", "quote": "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."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://www.proteomexchange.org) via the PRIDE partner repository [40] with the dataset identifier PXD000963 and doi 10.6019/PXD000963.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26388710", "locator": "sections[8] \"Mass spectrometry and database searches\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://www.proteomexchange.org) via the PRIDE partner repository [40] with the dataset identifier PXD000963 and doi 10.6019/PXD000963."}], "state": "complete"}, {"id": "claim-target-result", "statement": "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).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:26388710", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Annexin A2 provided the best prediction of risk of metastatic disease (log-rank Chi squared p = 0. 025)."}, {"asset": "source:pmid:26388710", "locator": "sections[2] \"Results and discussion\" paragraph 4", "quote": "Tumor and control tissue regions excised from FFPE sections from 16 patients, independent of tissue used for the prior MS analyses, were examined using a multiplexing method."}, {"asset": "source:pmid:26388710", "locator": "sections[2] \"Results and discussion\" paragraph 6", "quote": "Multivariate analysis, using Cox proportional hazard modeling was applied to explore the relationship between the relative abundance change of each protein, modeled as continuous variables, and time to biochemical failure at the same time controlling for any difference in treatment employed (Table 1)."}, {"asset": "source:pmid:26388710", "locator": "sections[2] \"Results and discussion\" paragraph 6", "quote": "Despite the small size of the dataset, and after controlling for all other protein relative abundance changes, the relative abundance change of ANXA2 in tumor versus control tissue was a significant and independent predictor of the risk of biochemical failure (p = 0.018)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "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).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:26388710"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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