Cargando…
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-...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783410725003198464 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6463201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT cristobalion deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT torrejonblanca deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT rubiojaime deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT santosandrea deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT pedregalmanuel deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT caramescristina deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT zazosandra deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT luquemelani deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT sanzalvarezmarta deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT madozgurpidejuan deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT rojofederico deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer AT garciafoncillasjesus deregulationofsetisassociatedwithtumorprogressionandpredictsadverseoutcomeinpatientswithearlystagecolorectalcancer |