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Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy

Preoperative neoadjuvant chemoradiotherapy (nCRT) is the gold standard in locally advanced rectal cancer, only 10–30% of patients achieving benefits. Currently, there is a need of a reliable selection of markers for the identification of poor or non-responders prior to therapy. In this work, we comp...

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Autores principales: Repetto, Ombretta, De Re, Valli, De Paoli, Antonino, Belluco, Claudio, Alessandrini, Lara, Canzonieri, Vincenzo, Cannizzaro, Renato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438653/
https://www.ncbi.nlm.nih.gov/pubmed/28423701
http://dx.doi.org/10.18632/oncotarget.16053
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author Repetto, Ombretta
De Re, Valli
De Paoli, Antonino
Belluco, Claudio
Alessandrini, Lara
Canzonieri, Vincenzo
Cannizzaro, Renato
author_facet Repetto, Ombretta
De Re, Valli
De Paoli, Antonino
Belluco, Claudio
Alessandrini, Lara
Canzonieri, Vincenzo
Cannizzaro, Renato
author_sort Repetto, Ombretta
collection PubMed
description Preoperative neoadjuvant chemoradiotherapy (nCRT) is the gold standard in locally advanced rectal cancer, only 10–30% of patients achieving benefits. Currently, there is a need of a reliable selection of markers for the identification of poor or non-responders prior to therapy. In this work, we compared protein profiles before therapy of patients differing in their responses to nCRT to find novel predictive markers of response to therapy. Patients were grouped into 3 groups according to their tumor regression grading (TRG) after surgery: 'TRG 1–2′, good responders, 'TRG 3′ and 'TRG 4′, poor responders. Paired surgical specimens of rectal cancer and healthy (histologically confirmed) rectal tissues from 15 patients were analysed before nCRT by two dimensional difference in gel electrophoresis followed by mass spectrometry. Thirty spots were found as differentially expressed (p < 0.05). Among them, 3 spots (spots 471, 683 and 684) showed an increased amount of protein in poor responders compared with good responders, and they were more tumor associated compared with healthy tissues. Proteins of these spots were identified as fibrinogen ß chain fragment D, actin isoforms, B9 and B5 serpins, cathepsin D isoforms and peroxiredoxin-4. In an independent validation set of 20 rectal carcinomas we validated the increased fibrinogen ß chain abundance before nCRT in poor responders by immunoblotting. In conclusion, we propose a risk-stratification tool in predicting the response to nCRT treatment in rectal cancer based on the quantity of these proteins.
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spelling pubmed-54386532017-05-24 Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy Repetto, Ombretta De Re, Valli De Paoli, Antonino Belluco, Claudio Alessandrini, Lara Canzonieri, Vincenzo Cannizzaro, Renato Oncotarget Research Paper Preoperative neoadjuvant chemoradiotherapy (nCRT) is the gold standard in locally advanced rectal cancer, only 10–30% of patients achieving benefits. Currently, there is a need of a reliable selection of markers for the identification of poor or non-responders prior to therapy. In this work, we compared protein profiles before therapy of patients differing in their responses to nCRT to find novel predictive markers of response to therapy. Patients were grouped into 3 groups according to their tumor regression grading (TRG) after surgery: 'TRG 1–2′, good responders, 'TRG 3′ and 'TRG 4′, poor responders. Paired surgical specimens of rectal cancer and healthy (histologically confirmed) rectal tissues from 15 patients were analysed before nCRT by two dimensional difference in gel electrophoresis followed by mass spectrometry. Thirty spots were found as differentially expressed (p < 0.05). Among them, 3 spots (spots 471, 683 and 684) showed an increased amount of protein in poor responders compared with good responders, and they were more tumor associated compared with healthy tissues. Proteins of these spots were identified as fibrinogen ß chain fragment D, actin isoforms, B9 and B5 serpins, cathepsin D isoforms and peroxiredoxin-4. In an independent validation set of 20 rectal carcinomas we validated the increased fibrinogen ß chain abundance before nCRT in poor responders by immunoblotting. In conclusion, we propose a risk-stratification tool in predicting the response to nCRT treatment in rectal cancer based on the quantity of these proteins. Impact Journals LLC 2017-03-09 /pmc/articles/PMC5438653/ /pubmed/28423701 http://dx.doi.org/10.18632/oncotarget.16053 Text en Copyright: © 2017 Repetto et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Repetto, Ombretta
De Re, Valli
De Paoli, Antonino
Belluco, Claudio
Alessandrini, Lara
Canzonieri, Vincenzo
Cannizzaro, Renato
Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy
title Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy
title_full Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy
title_fullStr Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy
title_full_unstemmed Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy
title_short Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy
title_sort identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemo-radiotherapy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438653/
https://www.ncbi.nlm.nih.gov/pubmed/28423701
http://dx.doi.org/10.18632/oncotarget.16053
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