Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemoradiotherapy

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6 Citations (Scopus)

Abstract

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 β 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 β 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.

Original languageEnglish
Pages (from-to)28328-28341
Number of pages14
JournalOncotarget
Volume8
Issue number17
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Chemoradiotherapy
Rectal Neoplasms
Neoplasm Grading
Neoplasms
Proteins
Protein Isoforms
Two-Dimensional Difference Gel Electrophoresis
Serpins
Peroxiredoxins
Cathepsin D
Neoadjuvant Therapy
Immunoblotting
Fibrinogen
Actins
Mass Spectrometry
Therapeutics
Carcinoma

Keywords

  • DIGE
  • Gastric diseases
  • Rectal cancer
  • Rectal proteomics
  • Tumor regression grade

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "Identification of protein clusters predictive of tumor response in rectal cancer patients receiving neoadjuvant chemoradiotherapy",
abstract = "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 β 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 β 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.",
keywords = "DIGE, Gastric diseases, Rectal cancer, Rectal proteomics, Tumor regression grade",
author = "Ombretta Repetto and {De Re}, Valli and {De Paoli}, Antonino and Claudio Belluco and Lara Alessandrini and Vincenzo Canzonieri and Renato Cannizzaro",
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AU - Repetto, Ombretta

AU - De Re, Valli

AU - De Paoli, Antonino

AU - Belluco, Claudio

AU - Alessandrini, Lara

AU - Canzonieri, Vincenzo

AU - Cannizzaro, Renato

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AB - 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 β 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 β 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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