Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/59331
Title: miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma
Author: Tejero Villalba, Rut
Navarro Ponz, Alfons
Campayo Guillaumes, Marc
Viñolas Segarra, Núria
Marrades Sicart, Ramon Ma.
Cordeiro Santanach, Anna
Ruíz-Martínez, Marc
Santasusagna, Sandra
Molins López-Rodó, Laureano
Ramírez, Josep
Monzó Planella, Mariano
Keywords: Migració cel·lular
Pronòstic mèdic
Histologia
Cell migration
Prognosis
Histology
Issue Date: Jul-2014
Publisher: Public Library of Science (PLoS)
Abstract: Several treatments in non-small cell lung cancer (NSCLC) are histology-dependent, and the need for histology-related markers is increasing. MicroRNAs (miRNAs) are promising molecular markers in multiple cancers and show differences in expression depending on histological subtype. The miRNA family miR-200 has been associated with the regulation of epithelial-mesenchymal (EMT)/mesenchymal-epithelial transition (MET). EMT involves profound phenotypic changes that include the loss of cell-cell adhesion, the loss of cell polarity, and the acquisition of migratory and invasive properties that facilitates metastasis. A dual role for the miR-200 family in the prognosis of several tumors has been related to tumor cell origin. However, the prognostic role and function of miR-200 family in early-stage NSCLC adenocarcinoma and squamous cell carcinoma (SCC) have not been well established. Methods: miRNA expression was determined using TaqMan assays in 155 tumors from resected NSCLC patients. Functional studies were conducted in three NSCLC cell lines: H23, A-549 and HCC-44. Results: High miR-200c expression was associated with shorter overall survival (OS) in the entire cohort (p = 0.024). High miR-200c (p = 0.0004) and miR-141 (p = 0.009) expression correlated with shorter OS in adenocarcinoma - but not in SCC. In the multivariate analysis, a risk score based on miR-141 and miR-200c expression emerged as an independent prognostic factor for OS in the entire cohort (OR, 2.787; p = 0.033) and in adenocarcinoma patients (OR, 10.649; p = 0.002). Functional analyses showed that miR-200c, was related to mesenchymal-epithelial transition (MET) and affected cell migration and E-cadherin levels, while overexpression of miR-141 reduced KLF6 protein levels and produced an increase of secretion of VEGFA in vitro (H23, p = 0.04; A-549, p = 0.03; HCC-44, p = 0.02) and was associated with higher blood microvessel density in patient tumor samples (p<0.001). Conclusion: High miR-141 and miR-200c expression are associated with shorter OS in NSCLC patients with adenocarcinoma through MET and angiogenesis.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0101899
It is part of: PLoS One, 2014, vol. 9, num. 7
Related resource: http://dx.doi.org/10.1371/journal.pone.0101899
URI: http://hdl.handle.net/2445/59331
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)

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