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Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error
BACKGROUND: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidit...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453845/ https://www.ncbi.nlm.nih.gov/pubmed/25032733 http://dx.doi.org/10.1038/bjc.2014.396 |
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author | Shipitsin, M Small, C Choudhury, S Giladi, E Friedlander, S Nardone, J Hussain, S Hurley, A D Ernst, C Huang, Y E Chang, H Nifong, T P Rimm, D L Dunyak, J Loda, M Berman, D M Blume-Jensen, P |
author_facet | Shipitsin, M Small, C Choudhury, S Giladi, E Friedlander, S Nardone, J Hussain, S Hurley, A D Ernst, C Huang, Y E Chang, H Nifong, T P Rimm, D L Dunyak, J Loda, M Berman, D M Blume-Jensen, P |
author_sort | Shipitsin, M |
collection | PubMed |
description | BACKGROUND: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. METHODS: Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a ‘high' and a ‘low' tumour microarray, respectively. RESULTS: Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. CONCLUSIONS: Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness. |
format | Online Article Text |
id | pubmed-4453845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44538452015-06-10 Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error Shipitsin, M Small, C Choudhury, S Giladi, E Friedlander, S Nardone, J Hussain, S Hurley, A D Ernst, C Huang, Y E Chang, H Nifong, T P Rimm, D L Dunyak, J Loda, M Berman, D M Blume-Jensen, P Br J Cancer Molecular Diagnostics BACKGROUND: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. METHODS: Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a ‘high' and a ‘low' tumour microarray, respectively. RESULTS: Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. CONCLUSIONS: Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness. Nature Publishing Group 2014-09-09 2014-07-17 /pmc/articles/PMC4453845/ /pubmed/25032733 http://dx.doi.org/10.1038/bjc.2014.396 Text en Copyright © 2014 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Molecular Diagnostics Shipitsin, M Small, C Choudhury, S Giladi, E Friedlander, S Nardone, J Hussain, S Hurley, A D Ernst, C Huang, Y E Chang, H Nifong, T P Rimm, D L Dunyak, J Loda, M Berman, D M Blume-Jensen, P Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error |
title | Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error |
title_full | Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error |
title_fullStr | Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error |
title_full_unstemmed | Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error |
title_short | Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error |
title_sort | identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error |
topic | Molecular Diagnostics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453845/ https://www.ncbi.nlm.nih.gov/pubmed/25032733 http://dx.doi.org/10.1038/bjc.2014.396 |
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