2026-06-14T03:30:02Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/74052024-11-29T20:54:16Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Martín-Sánchez, Esperanza
author
Mendaza, Saioa
author
Ulazia-Garmendia, Ane
author
Monreal-Santesteban, Iñaki
author
Blanco-Luquin, Idoia
author
Córdoba, Alicia
author
Vicente-García, Francisco
author
Pérez-Janices, Noemí
author
Escors, David
author
Megias Vazquez, Diego
author
López-Serra, Paula
author
Esteller, Manel
author
Illarramendi, José Juan
author
Guerrero-Setas, David
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ikerbasque - Basque Foundation for Science
funder
Fundación La Caixa
funder
SARAY: Asociación Navarra de Cáncer de Mama
funder
Ministerio de Economía y Competitividad (España)
funder
Institució Catalana de Recerca i Estudis Avançats
2019-03-27T11:26:59Z
2019-03-27T11:26:59Z
2017-02-28
Oncotarget. 2017;8(9):15789-15801.
10.18632/oncotarget.15004
1949-2553
1949-2553
Oncotarget
28178655
http://hdl.handle.net/20.500.12105/7405
The CHL1 gene encodes a cell-adhesion molecule proposed as being a putative tumour-suppressor gene in breast cancer (BC). However, neither the underlying molecular mechanisms nor the clinical value of CHL1 downregulation in BC has been explored. The methylation status of three CpG sites in the CHL1 promoter was analysed by pyrosequencing in neoplastic biopsies from 142 patients with invasive BC and compared with that of non-neoplastic tissues. We found higher CHL1 methylation levels in breast tumours than in non-neoplastic tissues, either from mammoplasties or adjacent-to-tumour, which correlated with lower levels of protein expression in tumours measured by immunohistochemistry. A panel of five BC cell lines was treated with two epigenetic drugs, and restoration of CHL1 expression was observed, indicating in vitro dynamic epigenetic regulation. CHL1 was silenced by shRNA in immortalized but non-neoplastic mammary cells, and enhanced cell proliferation and migration, but not invasion, were found by real-time cell analysis. The prognostic value of CHL1 hypermethylation was assessed by the log-rank test and fitted in a Cox regression model. Importantly, CHL1 hypermethylation was very significantly associated with shorter progression-free survival in our BC patient series, independent of age and stage (p = 0.001). In conclusion, our results indicate that CHL1 is downregulated by hypermethylation and that this epigenetic alteration is an independent prognostic factor in BC.
eng
CHL1
DNA methylation
breast cancer
prognostic biomarker
CHL1 hypermethylation as a potential biomarker of poor prognosis in breast cancer
journal article
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CHL1hypermethylationasapotential_2017.pdf.txt
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