Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/111222
Title: Epigenetic alterations leading to TMPRSS4 promoter hypomethylation and protein overexpression predict poor prognosis in squamous lung cancer patients
Author: Villalba, Maria
Diaz-Lagares, Angel
Redrado, Miriam
Aberasturi, Arrate L. de
Segura, Victor
Bodegas, Maria Elena
Pajares, Maria J.
Pio, Ruben
Freire, Javier
Gomez-Roman, Javier
Montuenga, Luis M.
Esteller, Manel
Sandoval, Juan
Calvo, Alfonso
Keywords: Epigènesi
ADN
Metilació
Marcadors tumorals
Dianes farmacològiques
Diagnòstic
Càncer de pulmó
Epigenesis
DNA
Methylation
Tumor markers
Drug targeting
Diagnosis
Lung cancer
Issue Date: 19-Apr-2016
Publisher: Impact Journals
Abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, which highlights the need of innovative therapeutic options. Although targeted therapies can be successfully used in a subset of patients with lung adenocarcinomas (ADC), they are not appropriate for patients with squamous cell carcinomas (SCC). In addition, there is an unmet need for the identification of prognostic biomarkers that can select patients at risk of relapse in early stages. Here, we have used several cohorts of NSCLC patients to analyze the prognostic value of both protein expression and DNA promoter methylation status of the prometastatic serine protease TMPRSS4. Moreover, expression and promoter methylation was evaluated in a panel of 46 lung cancer cell lines. We have demonstrated that a high TMPRSS4 expression is an independent prognostic factor in SCC. Similarly, aberrant hypomethylation in tumors, which correlates with high TMPRSS4 expression, is an independent prognostic predictor in SCC. The inverse correlation between expression and methylation status was also observed in cell lines. In vitro studies showed that treatment of cells lacking TMPRSS4 expression with a demethylating agent significantly increased TMPRSS4 levels. In conclusion, TMPRSS4 is a novel independent prognostic biomarker regulated by epigenetic changes in SCC and a potential therapeutic target in this tumor type, where targeted therapy is still underdeveloped.
Note: Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.8045
It is part of: Oncotarget, 2016, vol. 7, num. 16, p. 22752-22769
Related resource: https://doi.org/10.18632/oncotarget.8045
URI: http://hdl.handle.net/2445/111222
ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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