High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients

We have previously shown that Met activation through the hepatocyte growth factor (HGF) increases tumorogenesis, induces epithelial-to-mesenchymal transition (EMT) and chemoresistance in SCLC. We sought to evaluate circulating HGF levels in SCLC patients and assess correlation with outcome and EMT f...

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Autores: Cañadas, Israel, Taus, Álvaro, González, Iria, Villanueva, Xavie, Gimeno, Javier, Pijuan, Lara, Dómine, Manuel, Sánchez-Font, Albert, Vollmer, Ivan, Menéndez, Silvia, Arpí, Oriol, Mojal, Sergio, Rojo, Federico, Rovira, Ana, Albanell Mestres, Joan, Arriola Aperribay, Edurne
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/57084
Acesso em linha:http://hdl.handle.net/10230/57084
http://dx.doi.org/10.18632/oncotarget.2124
Access Level:acceso abierto
Palavra-chave:Small cell lung cancer
Hepatocyte growth factor
Met
Epithelial to mesenchymal transition
Chemoresistance
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spelling High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patientsCañadas, IsraelTaus, ÁlvaroGonzález, IriaVillanueva, XavieGimeno, JavierPijuan, LaraDómine, ManuelSánchez-Font, AlbertVollmer, IvanMenéndez, SilviaArpí, OriolMojal, SergioRojo, FedericoRovira, AnaAlbanell Mestres, JoanArriola Aperribay, EdurneSmall cell lung cancerHepatocyte growth factorMetEpithelial to mesenchymal transitionChemoresistanceWe have previously shown that Met activation through the hepatocyte growth factor (HGF) increases tumorogenesis, induces epithelial-to-mesenchymal transition (EMT) and chemoresistance in SCLC. We sought to evaluate circulating HGF levels in SCLC patients and assess correlation with outcome and EMT features in the tumor. Serum samples from patients with SCLC were prospectively obtained at diagnosis, response evaluation and progression. HGF serum (sHGF) was quantified by ELISA. EMT markers and p-Met/Met were assayed by immunohistochemistry in tumor samples. Clinical data were prospectively recorder. One-hundred twelve patients were included. High baseline levels of sHGF were associated with shorter overall survival (p=0.007) and remained independently associated with survival in the multivariate analysis (p=0.016). For stage IV patients, an increase of sHGF levels at response evaluation (p=0.042) and at progression (p=0.003) were associated with poor outcome. sHGF levels were associated (p<0.05) with a mesenchymal phenotype in the tumor. In conclusion, high sHGF at diagnosis and increases during the course of the disease predict for poor outcome in SCLC patients and associate with EMT in the tumor. These data provide novel evidence on a role of sHGF in the adverse clinical behavior of SCLC and support testing Met inhibitors in patients with high sHGF.Impact Journal202320232014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/57084http://dx.doi.org/10.18632/oncotarget.2124reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésOncotarget. 2014 Jun 20;5(14):5246-56All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.http://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/570842026-06-12T07:21:37Z
dc.title.none.fl_str_mv High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients
title High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients
spellingShingle High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients
Cañadas, Israel
Small cell lung cancer
Hepatocyte growth factor
Met
Epithelial to mesenchymal transition
Chemoresistance
title_short High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients
title_full High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients
title_fullStr High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients
title_full_unstemmed High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients
title_sort High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients
dc.creator.none.fl_str_mv Cañadas, Israel
Taus, Álvaro
González, Iria
Villanueva, Xavie
Gimeno, Javier
Pijuan, Lara
Dómine, Manuel
Sánchez-Font, Albert
Vollmer, Ivan
Menéndez, Silvia
Arpí, Oriol
Mojal, Sergio
Rojo, Federico
Rovira, Ana
Albanell Mestres, Joan
Arriola Aperribay, Edurne
author Cañadas, Israel
author_facet Cañadas, Israel
Taus, Álvaro
González, Iria
Villanueva, Xavie
Gimeno, Javier
Pijuan, Lara
Dómine, Manuel
Sánchez-Font, Albert
Vollmer, Ivan
Menéndez, Silvia
Arpí, Oriol
Mojal, Sergio
Rojo, Federico
Rovira, Ana
Albanell Mestres, Joan
Arriola Aperribay, Edurne
author_role author
author2 Taus, Álvaro
González, Iria
Villanueva, Xavie
Gimeno, Javier
Pijuan, Lara
Dómine, Manuel
Sánchez-Font, Albert
Vollmer, Ivan
Menéndez, Silvia
Arpí, Oriol
Mojal, Sergio
Rojo, Federico
Rovira, Ana
Albanell Mestres, Joan
Arriola Aperribay, Edurne
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Small cell lung cancer
Hepatocyte growth factor
Met
Epithelial to mesenchymal transition
Chemoresistance
topic Small cell lung cancer
Hepatocyte growth factor
Met
Epithelial to mesenchymal transition
Chemoresistance
description We have previously shown that Met activation through the hepatocyte growth factor (HGF) increases tumorogenesis, induces epithelial-to-mesenchymal transition (EMT) and chemoresistance in SCLC. We sought to evaluate circulating HGF levels in SCLC patients and assess correlation with outcome and EMT features in the tumor. Serum samples from patients with SCLC were prospectively obtained at diagnosis, response evaluation and progression. HGF serum (sHGF) was quantified by ELISA. EMT markers and p-Met/Met were assayed by immunohistochemistry in tumor samples. Clinical data were prospectively recorder. One-hundred twelve patients were included. High baseline levels of sHGF were associated with shorter overall survival (p=0.007) and remained independently associated with survival in the multivariate analysis (p=0.016). For stage IV patients, an increase of sHGF levels at response evaluation (p=0.042) and at progression (p=0.003) were associated with poor outcome. sHGF levels were associated (p<0.05) with a mesenchymal phenotype in the tumor. In conclusion, high sHGF at diagnosis and increases during the course of the disease predict for poor outcome in SCLC patients and associate with EMT in the tumor. These data provide novel evidence on a role of sHGF in the adverse clinical behavior of SCLC and support testing Met inhibitors in patients with high sHGF.
publishDate 2014
dc.date.none.fl_str_mv 2014
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/57084
http://dx.doi.org/10.18632/oncotarget.2124
url http://hdl.handle.net/10230/57084
http://dx.doi.org/10.18632/oncotarget.2124
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Oncotarget. 2014 Jun 20;5(14):5246-56
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journal
publisher.none.fl_str_mv Impact Journal
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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