Mendaza Lainez, Saioa

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https://academica-e.unavarra.es/handle/2454/49563

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Mendaza Lainez

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Saioa

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Ciencias de la Salud

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750455

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811567

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Author: Ulazia Garmendia, Ane × Subject: Breast cancer ×

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Now showing 1 - 2 of 2
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    PublicationOpen Access
    CDH22 hypermethylation is an independent prognostic biomarker in breast cancer
    (BioMed Central, 2017) Martín Sánchez, Esperanza; Mendaza Lainez, Saioa; Ulazia Garmendia, Ane; Monreal Santesteban, Iñaki; Córdoba Iturriagagoitia, Alicia; Vicente García, Francisco; Blanco Luquin, Idoia; Cruz, Susana de la; Aramendia, Ana; Guerrero Setas, David; Ciencias de la Salud; Osasun Zientziak
    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.
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    PublicationOpen Access
    CHL1 hypermethylation as a potential biomarker of poor prognosis in breast cancer
    (Impact Journals, 2017) Martín Sánchez, Esperanza; Mendaza Lainez, Saioa; Ulazia Garmendia, Ane; Monreal Santesteban, Iñaki; Blanco Luquin, Idoia; Córdoba Iturriagagoitia, Alicia; Vicente García, Francisco; Pérez Janices, Noemi; Escors Murugarren, David; Megías, Diego; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
    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.