Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer

Objectives: Tumor associated fibroblasts (TAFs) are essential contributors of the progression of non-small cell lung cancer (NSCLC). Most lung TAFs exhibit an activated phenotype characterized by the expression of α-SMA and fibrillar collagens. However, the prognostic value of these activation marke...

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Autores: Alcaraz, Jordi, Carrasco, Josep Lluís, Millares, Laura, Luis, Iuliana-Cristiana, Fernández-Porras, Francisco J., Martínez-Romero, Anabel, Diaz-Valdivia, Natalia, Sánchez de Cos, Julio, Rami-Porta, Ramón, Seijo, Luis, Ramírez, Josep, Pajares, María José, Reguart, Noemí, Barreiro Portela, Esther, Monsó Molas, Eduard
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/43756
Acceso en línea:http://hdl.handle.net/10230/43756
http://dx.doi.org/10.1016/j.lungcan.2019.07.020
Access Level:acceso abierto
Palabra clave:Cancer associated fibroblast
Collagen
Lung cancer
Necrosis
α-SMA
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spelling Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancerAlcaraz, JordiCarrasco, Josep LluísMillares, LauraLuis, Iuliana-CristianaFernández-Porras, Francisco J.Martínez-Romero, AnabelDiaz-Valdivia, NataliaSánchez de Cos, JulioRami-Porta, RamónSeijo, LuisRamírez, JosepPajares, María JoséReguart, NoemíBarreiro Portela, EstherMonsó Molas, EduardCancer associated fibroblastCollagenLung cancerNecrosisα-SMAObjectives: Tumor associated fibroblasts (TAFs) are essential contributors of the progression of non-small cell lung cancer (NSCLC). Most lung TAFs exhibit an activated phenotype characterized by the expression of α-SMA and fibrillar collagens. However, the prognostic value of these activation markers in NSCLC remains unclear. Material and methods: We conducted a quantitative image analysis of α-SMA immunostaining and picrosirius red staining of fibrillar collagens imaged by bright-field and polarized microscopy, respectively, using tissue microarrays with samples from 220 surgical patients, which elicited a percentage of positive staining area for each marker and patient. Results: Kaplan-Meier curves showed that all TAF activation markers were significantly associated with poor survival, and their prognostic value was independent of TNM staging as revealed by multivariate analysis, which elicited an adjusted increased risk of death after 3 years of 129% and 94% for fibrillar collagens imaged with bright-field (p = 0.004) and polarized light (p = 0.003), respectively, and of 89% for α-SMA (p = 0.009). We also found a significant association between all TAF activation markers and tumor necrosis, which is often indicative of hypoxia, supporting a pathologic link between tumor desmoplasia and necrosis/hypoxia. Conclusions: Our findings identify patients with large histologic coverage of fibrillar collagens and α-SMA + TAFs to be at higher risk of recurrence and death, supporting that they could be considered for adjuvant therapy.This work was further supported bygrants from the Ministerio de Economía y Competitividad (MINECO/FEDER, UE) (PI13/02368 and SAF2016-79527-R to JA, FIS 12/02040to EM and FIS 12/02534 to EB), Fundació Privada Cellex (to JA),Generalitat de Catalunya AGAUR (SGR 661 to JA, SGR 801 to EM),Junta Provincial de Barcelona de l’Associació Espanyola Contra elCàncer (AECC B16-917 to JA), Fundació Catalana de Pneumologia (toEM), Sociedad Española de Neumología y Cirugía Torácica–SEPAR (PIIOncología Torácica to EM, < /GN6 > SEPAR 437 < /GN6 > to NR),and beca CONICYT (to N.D-V.)Elsevier202020202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/43756http://dx.doi.org/10.1016/j.lungcan.2019.07.020reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésLung cancer. 2019 Sep;135:51-160info:eu-repo/grantAgreement/ES/1PE/SAF2016-79527-R0169-5002/ © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/437562026-06-12T07:21:37Z
dc.title.none.fl_str_mv Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer
title Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer
spellingShingle Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer
Alcaraz, Jordi
Cancer associated fibroblast
Collagen
Lung cancer
Necrosis
α-SMA
title_short Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer
title_full Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer
title_fullStr Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer
title_full_unstemmed Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer
title_sort Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer
dc.creator.none.fl_str_mv Alcaraz, Jordi
Carrasco, Josep Lluís
Millares, Laura
Luis, Iuliana-Cristiana
Fernández-Porras, Francisco J.
Martínez-Romero, Anabel
Diaz-Valdivia, Natalia
Sánchez de Cos, Julio
Rami-Porta, Ramón
Seijo, Luis
Ramírez, Josep
Pajares, María José
Reguart, Noemí
Barreiro Portela, Esther
Monsó Molas, Eduard
author Alcaraz, Jordi
author_facet Alcaraz, Jordi
Carrasco, Josep Lluís
Millares, Laura
Luis, Iuliana-Cristiana
Fernández-Porras, Francisco J.
Martínez-Romero, Anabel
Diaz-Valdivia, Natalia
Sánchez de Cos, Julio
Rami-Porta, Ramón
Seijo, Luis
Ramírez, Josep
Pajares, María José
Reguart, Noemí
Barreiro Portela, Esther
Monsó Molas, Eduard
author_role author
author2 Carrasco, Josep Lluís
Millares, Laura
Luis, Iuliana-Cristiana
Fernández-Porras, Francisco J.
Martínez-Romero, Anabel
Diaz-Valdivia, Natalia
Sánchez de Cos, Julio
Rami-Porta, Ramón
Seijo, Luis
Ramírez, Josep
Pajares, María José
Reguart, Noemí
Barreiro Portela, Esther
Monsó Molas, Eduard
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cancer associated fibroblast
Collagen
Lung cancer
Necrosis
α-SMA
topic Cancer associated fibroblast
Collagen
Lung cancer
Necrosis
α-SMA
description Objectives: Tumor associated fibroblasts (TAFs) are essential contributors of the progression of non-small cell lung cancer (NSCLC). Most lung TAFs exhibit an activated phenotype characterized by the expression of α-SMA and fibrillar collagens. However, the prognostic value of these activation markers in NSCLC remains unclear. Material and methods: We conducted a quantitative image analysis of α-SMA immunostaining and picrosirius red staining of fibrillar collagens imaged by bright-field and polarized microscopy, respectively, using tissue microarrays with samples from 220 surgical patients, which elicited a percentage of positive staining area for each marker and patient. Results: Kaplan-Meier curves showed that all TAF activation markers were significantly associated with poor survival, and their prognostic value was independent of TNM staging as revealed by multivariate analysis, which elicited an adjusted increased risk of death after 3 years of 129% and 94% for fibrillar collagens imaged with bright-field (p = 0.004) and polarized light (p = 0.003), respectively, and of 89% for α-SMA (p = 0.009). We also found a significant association between all TAF activation markers and tumor necrosis, which is often indicative of hypoxia, supporting a pathologic link between tumor desmoplasia and necrosis/hypoxia. Conclusions: Our findings identify patients with large histologic coverage of fibrillar collagens and α-SMA + TAFs to be at higher risk of recurrence and death, supporting that they could be considered for adjuvant therapy.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
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/10230/43756
http://dx.doi.org/10.1016/j.lungcan.2019.07.020
url http://hdl.handle.net/10230/43756
http://dx.doi.org/10.1016/j.lungcan.2019.07.020
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Lung cancer. 2019 Sep;135:51-160
info:eu-repo/grantAgreement/ES/1PE/SAF2016-79527-R
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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