Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer

Despite distant metastases being the critical factor affecting patients' survival, they remain poorly understood. Our study thus aimed to molecularly characterize colorectal cancer liver metastases (CRCLMs) and explore whether molecular profiles differ between Synchronous (SmCRC) and Metachrono...

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Autores: Horak, Josef, Kubecek, Ondrej, Siskova, Anna, Honkova, Katerina, Chvojkova, Irena, Krupova, Marketa, Manethova, Monika, Vodenkova, Sona, García Mulero, Sandra, John, Stanislav, Cecka, Filip, Vodickova, Ludmila, Petera, Jiri, Filip, Stanislav, Vymetalkova, Veronika
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/200908
Acceso en línea:https://hdl.handle.net/2445/200908
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Metàstasi
Fetge
Colorectal cancer
Metastasis
Liver
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repository_id_str
spelling Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancerHorak, JosefKubecek, OndrejSiskova, AnnaHonkova, KaterinaChvojkova, IrenaKrupova, MarketaManethova, MonikaVodenkova, SonaGarcía Mulero, SandraJohn, StanislavCecka, FilipVodickova, LudmilaPetera, JiriFilip, StanislavVymetalkova, VeronikaCàncer colorectalMetàstasiFetgeColorectal cancerMetastasisLiverDespite distant metastases being the critical factor affecting patients' survival, they remain poorly understood. Our study thus aimed to molecularly characterize colorectal cancer liver metastases (CRCLMs) and explore whether molecular profiles differ between Synchronous (SmCRC) and Metachronous (MmCRC) colorectal cancer. This characterization was performed by whole exome sequencing, whole transcriptome, whole methylome, and miRNAome. The most frequent somatic mutations were in APC, SYNE1, TP53, and TTN genes. Among the differently methylated and expressed genes were those involved in cell adhesion, extracellular matrix organization and degradation, neuroactive ligand-receptor interaction. The top up-regulated microRNAs were hsa-miR-135b-3p and -5p, and the hsa-miR-200-family while the hsa-miR-548-family belonged to the top down-regulated. MmCRC patients evinced higher tumor mutational burden, a wider median of duplications and deletions, and a heterogeneous mutational signature than SmCRC. Regarding chronicity, a significant down-regulation of SMOC2 and PPP1R9A genes in SmCRC compared to MmCRC was observed. Two miRNAs were deregulated between SmCRC and MmCRC, hsa-miR-625-3p and has-miR-1269-3p. The combined data identified the IPO5 gene. Regardless of miRNA expression levels, the combined analysis resulted in 107 deregulated genes related to relaxin, estrogen, PI3K-Akt, WNT signaling pathways, and intracellular second messenger signaling. The intersection between our and validation sets confirmed the validity of our results. We have identified genes and pathways that may be considered as actionable targets in CRCLMs. Our data also provide a valuable resource for understanding molecular distinctions between SmCRC and MmCRC. They have the potential to enhance the diagnosis, prognostication, and management of CRCLMs by a molecularly targeted approach.Frontiers Media SA2023202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/200908Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3389/fonc.2023.1133598Frontiers in Oncology, 2023, vol. 13https://doi.org/10.3389/fonc.2023.1133598cc by (c) Horak, Josef et al, 2023http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2009082026-05-29T05:05:01Z
dc.title.none.fl_str_mv Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer
title Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer
spellingShingle Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer
Horak, Josef
Càncer colorectal
Metàstasi
Fetge
Colorectal cancer
Metastasis
Liver
title_short Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer
title_full Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer
title_fullStr Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer
title_full_unstemmed Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer
title_sort Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer
dc.creator.none.fl_str_mv Horak, Josef
Kubecek, Ondrej
Siskova, Anna
Honkova, Katerina
Chvojkova, Irena
Krupova, Marketa
Manethova, Monika
Vodenkova, Sona
García Mulero, Sandra
John, Stanislav
Cecka, Filip
Vodickova, Ludmila
Petera, Jiri
Filip, Stanislav
Vymetalkova, Veronika
author Horak, Josef
author_facet Horak, Josef
Kubecek, Ondrej
Siskova, Anna
Honkova, Katerina
Chvojkova, Irena
Krupova, Marketa
Manethova, Monika
Vodenkova, Sona
García Mulero, Sandra
John, Stanislav
Cecka, Filip
Vodickova, Ludmila
Petera, Jiri
Filip, Stanislav
Vymetalkova, Veronika
author_role author
author2 Kubecek, Ondrej
Siskova, Anna
Honkova, Katerina
Chvojkova, Irena
Krupova, Marketa
Manethova, Monika
Vodenkova, Sona
García Mulero, Sandra
John, Stanislav
Cecka, Filip
Vodickova, Ludmila
Petera, Jiri
Filip, Stanislav
Vymetalkova, Veronika
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Metàstasi
Fetge
Colorectal cancer
Metastasis
Liver
topic Càncer colorectal
Metàstasi
Fetge
Colorectal cancer
Metastasis
Liver
description Despite distant metastases being the critical factor affecting patients' survival, they remain poorly understood. Our study thus aimed to molecularly characterize colorectal cancer liver metastases (CRCLMs) and explore whether molecular profiles differ between Synchronous (SmCRC) and Metachronous (MmCRC) colorectal cancer. This characterization was performed by whole exome sequencing, whole transcriptome, whole methylome, and miRNAome. The most frequent somatic mutations were in APC, SYNE1, TP53, and TTN genes. Among the differently methylated and expressed genes were those involved in cell adhesion, extracellular matrix organization and degradation, neuroactive ligand-receptor interaction. The top up-regulated microRNAs were hsa-miR-135b-3p and -5p, and the hsa-miR-200-family while the hsa-miR-548-family belonged to the top down-regulated. MmCRC patients evinced higher tumor mutational burden, a wider median of duplications and deletions, and a heterogeneous mutational signature than SmCRC. Regarding chronicity, a significant down-regulation of SMOC2 and PPP1R9A genes in SmCRC compared to MmCRC was observed. Two miRNAs were deregulated between SmCRC and MmCRC, hsa-miR-625-3p and has-miR-1269-3p. The combined data identified the IPO5 gene. Regardless of miRNA expression levels, the combined analysis resulted in 107 deregulated genes related to relaxin, estrogen, PI3K-Akt, WNT signaling pathways, and intracellular second messenger signaling. The intersection between our and validation sets confirmed the validity of our results. We have identified genes and pathways that may be considered as actionable targets in CRCLMs. Our data also provide a valuable resource for understanding molecular distinctions between SmCRC and MmCRC. They have the potential to enhance the diagnosis, prognostication, and management of CRCLMs by a molecularly targeted approach.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
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 https://hdl.handle.net/2445/200908
url https://hdl.handle.net/2445/200908
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/10.3389/fonc.2023.1133598
Frontiers in Oncology, 2023, vol. 13
https://doi.org/10.3389/fonc.2023.1133598
dc.rights.none.fl_str_mv cc by (c) Horak, Josef et al, 2023
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Horak, Josef et al, 2023
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 16 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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