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Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer

SET nuclear proto-oncogene (SET) deregulation is a novel molecular target in metastatic colorectal cancer (CRC). However, its role in CRC progression and its potential clinical impact in early-stage CRC patients remain unknown. Here, we studied the biological effects of SET on migration using wound-...

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Autores principales: Cristóbal, Ion, Torrejón, Blanca, Rubio, Jaime, Santos, Andrea, Pedregal, Manuel, Caramés, Cristina, Zazo, Sandra, Luque, Melani, Sanz-Alvarez, Marta, Madoz-Gúrpide, Juan, Rojo, Federico, García-Foncillas, Jesús
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463201/
https://www.ncbi.nlm.nih.gov/pubmed/30871013
http://dx.doi.org/10.3390/jcm8030346
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author Cristóbal, Ion
Torrejón, Blanca
Rubio, Jaime
Santos, Andrea
Pedregal, Manuel
Caramés, Cristina
Zazo, Sandra
Luque, Melani
Sanz-Alvarez, Marta
Madoz-Gúrpide, Juan
Rojo, Federico
García-Foncillas, Jesús
author_facet Cristóbal, Ion
Torrejón, Blanca
Rubio, Jaime
Santos, Andrea
Pedregal, Manuel
Caramés, Cristina
Zazo, Sandra
Luque, Melani
Sanz-Alvarez, Marta
Madoz-Gúrpide, Juan
Rojo, Federico
García-Foncillas, Jesús
author_sort Cristóbal, Ion
collection PubMed
description SET nuclear proto-oncogene (SET) deregulation is a novel molecular target in metastatic colorectal cancer (CRC). However, its role in CRC progression and its potential clinical impact in early-stage CRC patients remain unknown. Here, we studied the biological effects of SET on migration using wound-healing and transwell assays, and anchorage-independent cell growth using soft agar colony formation assays after ectopic SET modulation. SET was analyzed by immuno-staining in 231 early-stage CRC patients, and miR-199b expression was quantified by real-time PCR in a set of CRC patients. Interestingly, SET enhances cell migration, markedly affects the colony-forming ability, promotes epithelial to mesenchymal transition, and induces the expression of the MYC proto-oncogene (c-MYC) in CRC cells. SET overexpression was detected in 15.4% of cases and was associated with worse Eastern Cooperative Oncology Group (ECOG) status (p = 0.021) and relapse in stage-II CRC patients (p = 0.008). Moreover, SET overexpression predicted shorter overall survival (p < 0.001) and time to metastasis (p < 0.001), and its prognostic value was particularly evident in elderly patients. MiR-199b downregulation was identified as a molecular mechanism to deregulate SET in patients with localized disease. In conclusion, SET overexpression is a common alteration in early-stage CRC, playing an oncogenic role associated with progression and aggressiveness, and portends a poor outcome. Thus, SET emerges as a novel potential molecular target with clinical impact in early-stage in CRC.
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spelling pubmed-64632012019-04-19 Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer Cristóbal, Ion Torrejón, Blanca Rubio, Jaime Santos, Andrea Pedregal, Manuel Caramés, Cristina Zazo, Sandra Luque, Melani Sanz-Alvarez, Marta Madoz-Gúrpide, Juan Rojo, Federico García-Foncillas, Jesús J Clin Med Article SET nuclear proto-oncogene (SET) deregulation is a novel molecular target in metastatic colorectal cancer (CRC). However, its role in CRC progression and its potential clinical impact in early-stage CRC patients remain unknown. Here, we studied the biological effects of SET on migration using wound-healing and transwell assays, and anchorage-independent cell growth using soft agar colony formation assays after ectopic SET modulation. SET was analyzed by immuno-staining in 231 early-stage CRC patients, and miR-199b expression was quantified by real-time PCR in a set of CRC patients. Interestingly, SET enhances cell migration, markedly affects the colony-forming ability, promotes epithelial to mesenchymal transition, and induces the expression of the MYC proto-oncogene (c-MYC) in CRC cells. SET overexpression was detected in 15.4% of cases and was associated with worse Eastern Cooperative Oncology Group (ECOG) status (p = 0.021) and relapse in stage-II CRC patients (p = 0.008). Moreover, SET overexpression predicted shorter overall survival (p < 0.001) and time to metastasis (p < 0.001), and its prognostic value was particularly evident in elderly patients. MiR-199b downregulation was identified as a molecular mechanism to deregulate SET in patients with localized disease. In conclusion, SET overexpression is a common alteration in early-stage CRC, playing an oncogenic role associated with progression and aggressiveness, and portends a poor outcome. Thus, SET emerges as a novel potential molecular target with clinical impact in early-stage in CRC. MDPI 2019-03-12 /pmc/articles/PMC6463201/ /pubmed/30871013 http://dx.doi.org/10.3390/jcm8030346 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cristóbal, Ion
Torrejón, Blanca
Rubio, Jaime
Santos, Andrea
Pedregal, Manuel
Caramés, Cristina
Zazo, Sandra
Luque, Melani
Sanz-Alvarez, Marta
Madoz-Gúrpide, Juan
Rojo, Federico
García-Foncillas, Jesús
Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer
title Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer
title_full Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer
title_fullStr Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer
title_full_unstemmed Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer
title_short Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer
title_sort deregulation of set is associated with tumor progression and predicts adverse outcome in patients with early-stage colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463201/
https://www.ncbi.nlm.nih.gov/pubmed/30871013
http://dx.doi.org/10.3390/jcm8030346
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