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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2017 - 20202
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Subject: Predictive biomarker ×

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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
    Absence of nuclear p16 is a diagnostic and independent prognostic biomarker in squamous cell carcinoma of the cervix
    (MDPI, 2020) Mendaza Lainez, Saioa; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Zudaire, Tamara; Guarch, Rosa; Guerrero Setas, David; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
    The tumor-suppressor protein p16 is paradoxically overexpressed in cervical cancer (CC). Despite its potential as a biomarker, its clinical value and the reasons for its failure in tumor suppression remain unclear. Our purpose was to determine p16 clinical and biological significance in CC. p16 expression pattern was examined by immunohistochemistry in 78 CC cases (high-grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas of the cervix –SCCCs). CC cell proliferation and invasion were monitored by real-time cell analysis and Transwell® invasion assay, respectively. Cytoplasmic p16 interactors were identified from immunoprecipitated extracts by liquid chromatography-tandem mass spectrometry, and colocalization was confirmed by double-immunofluorescence. We observed that SCCCs showed significantly more cytoplasmic than nuclear p16 expression than HSILs. Importantly, nuclear p16 absence significantly predicted poor outcome in SCCC patients irrespective of other clinical parameters. Moreover, we demonstrated that cytoplasmic p16 interacted with CDK4 and other unreported proteins, such as BANF1, AKAP8 and AGTRAP, which could sequester p16 to avoid nuclear translocation, and then, impair its anti-tumor function. Our results suggest that the absence of nuclear p16 could be a diagnostic biomarker between HSIL and SCCC, and an independent prognostic biomarker in SCCC; and explain why p16 overexpression fails to stop CC growth.