ZEB1 hypermethylation is associated with better prognosis in patients with colon cancer

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dc.contributor.authorFernández de los Reyes, Irene
dc.contributor.authorGómez Dorronsoro, María Luisa
dc.contributor.authorMonreal Santesteban, Iñaki
dc.contributor.authorFernández-Fernández, Agustín
dc.contributor.authorFraga, Mario
dc.contributor.authorAzcue Sanromán, Pablo
dc.contributor.authorAlonso, Laura
dc.contributor.authorFernández-Marlasca, Beatriz
dc.contributor.authorSuárez Alecha, Javier
dc.contributor.authorCórdoba Iturriagagoitia, Alicia
dc.contributor.authorGuerrero Setas, David
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderUniversidad Pública de Navarra / Nafarroako Unibertsitate Publikoaes
dc.date.accessioned2024-05-03T16:04:26Z
dc.date.available2024-05-03T16:04:26Z
dc.date.issued2023
dc.date.updated2024-05-03T15:06:18Z
dc.description.abstractBackground: Colon cancer (CC) is a heterogeneous disease that is categorized into four Consensus Molecular Subtypes (CMS) according to gene expression. Patients with loco-regional CC (stages II/III) lack prognostic factors, making it essential to analyze new molecular markers that can delineate more aggressive tumors. Aberrant methylation of genes that are essential in crucial mechanisms such as epithelial mesenchymal transition (EMT) contributes to tumor progression in CC. We evaluate the presence of hyper- and hypomethylation in subrogate IHC markers used for CMS classification (CDX2, FRMD6, HTR2B, ZEB1) of 144 stage II/III patients and CC cell lines by pyrosequencing. ZEB1 expression was also studied in control and shRNA-silenced CC cell lines and in paired normal tissue/tumors by quantitative PCR. The pattern of ZEB1 staining was also analyzed in methylated/unmethylated tumors by immunohistochemistry. Results: We describe for the first time the hypermethylation of ZEB1 gene and the hypomethylation of the FRMD6 gene in 32.6% and 50.9% of tumors, respectively. Additionally, we confirm the ZEB1 re-expression by epigenetic drugs in methylated cell lines. ZEB1 hypermethylation was more frequent in CMS1 patients and, more importantly, was a good prognostic factor related to disease-free survival (p = 0.015) and overall survival (p = 0.006) in our patient series, independently of other significant clinical parameters such as patient age, stage, lymph node involvement, and blood vessel and perineural invasión. Conclusions: Aberrant methylation is present in the subrogate genes used for CMS classification. Our results are the first evidence that ZEB1 is hypermethylated in CC and that this alteration is an independent factor of good prognosis.en
dc.description.sponsorshipOpen Access funding provided by Universidad Pública de Navarra. This research was funded by European Union Regional Development Fund (17–20, RefBioII, Trans-Pyrenean cooperation network program 2016–2018, INTERREG-POCTEFA) https://ec.europa.eu/regional_policy/en/funding/erdf/.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationFernandez-De-Los-Reyes, I., Gomez-Dorronsoro, M., Monreal-Santesteban, I., Fernandez-Fernandez, A., Fraga, M., Azcue, P., Alonso, L., Fernandez-Marlasca, B., Suarez, J., Cordoba-Iturriagagoitia, A., Guerrero-Setas, D. (2023) ZEB1 hypermethylation is associated with better prognosis in patients with colon cancer. Clinical Epigenetics, 15(1), 1-13. https://doi.org/10.1186/s13148-023-01605-7.en
dc.identifier.doi10.1186/s13148-023-01605-7
dc.identifier.issn1868-7075
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/48051
dc.language.isoengen
dc.publisherBMCen
dc.relation.ispartofClinical Epigenetics 2023, 15(1), 193, 1-13en
dc.relation.publisherversionhttps://doi.org/10.1186/s13148-023-01605-7
dc.rights© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCMSen
dc.subjectColon canceren
dc.subjectDNA methylationen
dc.subjectPrognostic biomarkeren
dc.titleZEB1 hypermethylation is associated with better prognosis in patients with colon canceren
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationcc2f7744-a121-49a2-9a45-d03e71bc8876
relation.isAuthorOfPublication.latestForDiscoverycc2f7744-a121-49a2-9a45-d03e71bc8876

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