CDH22 hypermethylation is an independent prognostic biomarker in breast cancer
| dc.contributor.author | Martín Sánchez, Esperanza | |
| dc.contributor.author | Mendaza Lainez, Saioa | |
| dc.contributor.author | Ulazia Garmendia, Ane | |
| dc.contributor.author | Monreal Santesteban, Iñaki | |
| dc.contributor.author | Córdoba Iturriagagoitia, Alicia | |
| dc.contributor.author | Vicente García, Francisco | |
| dc.contributor.author | Blanco Luquin, Idoia | |
| dc.contributor.author | Cruz, Susana de la | |
| dc.contributor.author | Aramendia, Ana | |
| dc.contributor.author | Guerrero Setas, David | |
| dc.contributor.department | Ciencias de la Salud | es_ES |
| dc.contributor.department | Osasun Zientziak | eu |
| dc.date.accessioned | 2018-10-23T07:35:33Z | |
| dc.date.available | 2018-10-23T07:35:33Z | |
| dc.date.issued | 2017 | |
| dc.description.abstract | Background: Cadherin-like protein 22 (CDH22) is a transmembrane glycoprotein involved in cell-cell adhesion and metastasis. Its role in cancer is controversial because it has been described as being upregulated in colorectal cancer, whereas it is downregulated in metastatic melanoma. However, its status in breast cancer (BC) is unknown. The purpose of our study was to determine the molecular status and clinical value of CDH22 in BC. Results: We observed by immunohistochemistry that the level of CDH22 expression was lower in BC tissues than in their matched adjacent-to-tumour and non-neoplastic tissues from reduction mammoplasties. Since epigenetic alteration is one of the main causes of gene silencing, we analysed the hypermethylation of 3 CpG sites in the CDH22 promoter by pyrosequencing in a series of 142 infiltrating duct BC cases. CDH22 was found to be hypermethylated in tumoral tissues relative to non-neoplastic mammary tissues. Importantly, this epigenetic alteration was already present in adjacent-to-tumour tissues, although to a lesser extent than in tumoral samples. Furthermore, CDH22 gene regulation was dynamically modulated in vitro by epigenetic drugs. Interestingly, CDH22 hypermethylation in all 3 CpG sites simultaneously, but not expression, was significantly associated with shorter progression-free survival (p = 0.015) and overall survival (p = 0.021) in our patient series. Importantly, CDH22 hypermethylation was an independent factor that predicts poor progression-free survival regardless of age and stage (p = 0.006). Conclusions: Our results are the first evidence that CDH22 is hypermethylated in BC and that this alteration is an independent prognostic factor in BC. Thus, CDH22 hypermethylation could be a potential biomarker of poor prognosis in BC. | en |
| dc.description.sponsorship | This work has been funded in competitive calls by the Spanish Institute of Health (PI14/00579), the Basque Foundation for Healthcare Research and Innovation (BIO-11-CM-013), La Caixa Foundation (70789) and the Breast Cancer Patients’ Association in Navarra (SARAY). EMS is the recipient of a grant from the Spanish Ministry of Economy and Competitiveness (PTA2015-11895-I). | en |
| dc.format.extent | 8 p. | |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | 10.1186/s13148-016-0309-z | |
| dc.identifier.issn | 1868-7075 (Print) | |
| dc.identifier.issn | 1868-7083 (Electronic) | |
| dc.identifier.uri | https://academica-e.unavarra.es/handle/2454/31121 | |
| dc.language.iso | eng | en |
| dc.publisher | BioMed Central | en |
| dc.relation.ispartof | Clinical Epigenetics (2017) 9:7 | en |
| dc.relation.publisherversion | https://doi.org/10.1186/s13148-016-0309-z | |
| dc.rights | © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated | en |
| dc.rights.accessRights | info:eu-repo/semantics/openAccess | |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
| dc.subject | CDH22 | en |
| dc.subject | DNA methylation | en |
| dc.subject | Breast cancer | en |
| dc.subject | Predictive biomarker | en |
| dc.title | CDH22 hypermethylation is an independent prognostic biomarker in breast cancer | en |
| dc.type | info:eu-repo/semantics/article | |
| dc.type.version | info:eu-repo/semantics/publishedVersion | |
| dspace.entity.type | Publication | |
| relation.isAuthorOfPublication | ab42c33f-1671-49dc-ab31-89b9cac82366 | |
| relation.isAuthorOfPublication.latestForDiscovery | ab42c33f-1671-49dc-ab31-89b9cac82366 |