Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis

To date, no systematic analyses are available assessing concordance of molecular classifications between primary tumors (PT) and matched liver metastases (LM) of metastatic colorectal cancer (mCRC). We investigated concordance between PT and LM for four clinically relevant CRC gene signatures. Twent...

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Autores: Schlicker, Andreas, Ellappalayam, Architha, Beumer, Inés J., Snel, Mireille H. J., Mittempergher, Lorenza, Diosdado, Begona, Dreezen, Christa, Tian, Sun, Salazar Soler, Ramón, Loupakis, Fotios, Pietrantonio, Filippo, Santos, Cristina, Martínez Villacampa, Mercedes, Villanueva Garatachea, Alberto, Sanjuan, Xavier, Schirripa, Marta, Fassan, Matteo, Martinetti, Antonia, Fucà, Giovanni, Lonardi, Sara, Keilholz, Ulrich, Glas, Annuska M., Bernards, René, Vecchione, Loredana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/174488
Acceso en línea:https://hdl.handle.net/2445/174488
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Metàstasi
Càncer de fetge
Expressió gènica
Colorectal cancer
Metastasis
Liver cancer
Gene expression
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spelling Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasisSchlicker, AndreasEllappalayam, ArchithaBeumer, Inés J.Snel, Mireille H. J.Mittempergher, LorenzaDiosdado, BegonaDreezen, ChristaTian, SunSalazar Soler, RamónLoupakis, FotiosPietrantonio, FilippoSantos, CristinaMartínez Villacampa, MercedesVillanueva Garatachea, AlbertoSanjuan, XavierSchirripa, MartaFassan, MatteoMartinetti, AntoniaFucà, GiovanniLonardi, SaraKeilholz, UlrichGlas, Annuska M.Bernards, RenéVecchione, LoredanaCàncer colorectalMetàstasiCàncer de fetgeExpressió gènicaColorectal cancerMetastasisLiver cancerGene expressionTo date, no systematic analyses are available assessing concordance of molecular classifications between primary tumors (PT) and matched liver metastases (LM) of metastatic colorectal cancer (mCRC). We investigated concordance between PT and LM for four clinically relevant CRC gene signatures. Twenty-seven fresh and 55 formalin-fixed paraffin-embedded pairs of PT and synchronous LM of untreated mCRC patients were retrospectively collected and classified according to the MSI-like, BRAF-like, TGFB activated-like and the Consensus Molecular Subtypes (CMS) classification. We investigated classification concordance between PT and LM and association of TGFBa-like and CMS classification with overall survival. Fifty-one successfully profiled matched pairs were used for analyses. PT and matched LM were highly concordant in terms of BRAF-like and MSI-like signatures, (90.2% and 98% concordance, respectively). In contrast, 40% to 70% of PT that were classified as mesenchymal-like, based on the CMS and the TGFBa-like signature, respectively, lost this phenotype in their matched LM (60.8% and 76.5% concordance, respectively). This molecular switch was independent of the microenvironment composition. In addition, the significant change in subtypes was observed also by using methods developed to detect cancer cell-intrinsic subtypes. More importantly, the molecular switch did not influence the survival. PT classified as mesenchymal had worse survival as compared to nonmesenchymal PT (CMS4 vs CMS2, hazard ratio [HR] = 5.2, 95% CI = 1.5-18.5, P = .0048; TGFBa-like vs TGFBi-like, HR = 2.5, 95% CI = 1.1-5.6, P = .028). The same was not true for LM. Our study highlights that the origin of the tissue may have major consequences for precision medicine in mCRC.Wiley2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/174488Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1002/ijc.33003International Journal of Cancer, 2020, vol. 147, p. 2303-2315https://doi.org/10.1002/ijc.33003cc by (c) Schlicker, Andreas et al., 2020http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1744882026-05-27T06:46:51Z
dc.title.none.fl_str_mv Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis
title Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis
spellingShingle Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis
Schlicker, Andreas
Càncer colorectal
Metàstasi
Càncer de fetge
Expressió gènica
Colorectal cancer
Metastasis
Liver cancer
Gene expression
title_short Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis
title_full Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis
title_fullStr Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis
title_full_unstemmed Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis
title_sort Investigating the Concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis
dc.creator.none.fl_str_mv Schlicker, Andreas
Ellappalayam, Architha
Beumer, Inés J.
Snel, Mireille H. J.
Mittempergher, Lorenza
Diosdado, Begona
Dreezen, Christa
Tian, Sun
Salazar Soler, Ramón
Loupakis, Fotios
Pietrantonio, Filippo
Santos, Cristina
Martínez Villacampa, Mercedes
Villanueva Garatachea, Alberto
Sanjuan, Xavier
Schirripa, Marta
Fassan, Matteo
Martinetti, Antonia
Fucà, Giovanni
Lonardi, Sara
Keilholz, Ulrich
Glas, Annuska M.
Bernards, René
Vecchione, Loredana
author Schlicker, Andreas
author_facet Schlicker, Andreas
Ellappalayam, Architha
Beumer, Inés J.
Snel, Mireille H. J.
Mittempergher, Lorenza
Diosdado, Begona
Dreezen, Christa
Tian, Sun
Salazar Soler, Ramón
Loupakis, Fotios
Pietrantonio, Filippo
Santos, Cristina
Martínez Villacampa, Mercedes
Villanueva Garatachea, Alberto
Sanjuan, Xavier
Schirripa, Marta
Fassan, Matteo
Martinetti, Antonia
Fucà, Giovanni
Lonardi, Sara
Keilholz, Ulrich
Glas, Annuska M.
Bernards, René
Vecchione, Loredana
author_role author
author2 Ellappalayam, Architha
Beumer, Inés J.
Snel, Mireille H. J.
Mittempergher, Lorenza
Diosdado, Begona
Dreezen, Christa
Tian, Sun
Salazar Soler, Ramón
Loupakis, Fotios
Pietrantonio, Filippo
Santos, Cristina
Martínez Villacampa, Mercedes
Villanueva Garatachea, Alberto
Sanjuan, Xavier
Schirripa, Marta
Fassan, Matteo
Martinetti, Antonia
Fucà, Giovanni
Lonardi, Sara
Keilholz, Ulrich
Glas, Annuska M.
Bernards, René
Vecchione, Loredana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Metàstasi
Càncer de fetge
Expressió gènica
Colorectal cancer
Metastasis
Liver cancer
Gene expression
topic Càncer colorectal
Metàstasi
Càncer de fetge
Expressió gènica
Colorectal cancer
Metastasis
Liver cancer
Gene expression
description To date, no systematic analyses are available assessing concordance of molecular classifications between primary tumors (PT) and matched liver metastases (LM) of metastatic colorectal cancer (mCRC). We investigated concordance between PT and LM for four clinically relevant CRC gene signatures. Twenty-seven fresh and 55 formalin-fixed paraffin-embedded pairs of PT and synchronous LM of untreated mCRC patients were retrospectively collected and classified according to the MSI-like, BRAF-like, TGFB activated-like and the Consensus Molecular Subtypes (CMS) classification. We investigated classification concordance between PT and LM and association of TGFBa-like and CMS classification with overall survival. Fifty-one successfully profiled matched pairs were used for analyses. PT and matched LM were highly concordant in terms of BRAF-like and MSI-like signatures, (90.2% and 98% concordance, respectively). In contrast, 40% to 70% of PT that were classified as mesenchymal-like, based on the CMS and the TGFBa-like signature, respectively, lost this phenotype in their matched LM (60.8% and 76.5% concordance, respectively). This molecular switch was independent of the microenvironment composition. In addition, the significant change in subtypes was observed also by using methods developed to detect cancer cell-intrinsic subtypes. More importantly, the molecular switch did not influence the survival. PT classified as mesenchymal had worse survival as compared to nonmesenchymal PT (CMS4 vs CMS2, hazard ratio [HR] = 5.2, 95% CI = 1.5-18.5, P = .0048; TGFBa-like vs TGFBi-like, HR = 2.5, 95% CI = 1.1-5.6, P = .028). The same was not true for LM. Our study highlights that the origin of the tissue may have major consequences for precision medicine in mCRC.
publishDate 2020
dc.date.none.fl_str_mv 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 https://hdl.handle.net/2445/174488
url https://hdl.handle.net/2445/174488
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1002/ijc.33003
International Journal of Cancer, 2020, vol. 147, p. 2303-2315
https://doi.org/10.1002/ijc.33003
dc.rights.none.fl_str_mv cc by (c) Schlicker, Andreas et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Schlicker, Andreas et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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