CDH22 hypermethylation is an independent prognostic biomarker in breast cancer
Fecha
2017Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión publicada / Argitaratu den bertsioa
Impacto
|
10.1186/s13148-016-0309-z
Resumen
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 s ...
[++]
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. [--]
Materias
CDH22,
DNA methylation,
Breast cancer,
Predictive biomarker
Editor
BioMed Central
Publicado en
Clinical Epigenetics (2017) 9:7
Departamento
Universidad Pública de Navarra. Departamento de Ciencias de la Salud /
Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Versión del editor
Entidades Financiadoras
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).
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