miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma.
<h4>Background</h4>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 histologic...
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oai:doaj.org-article:959f3298dafd4a1e9d1cc38ea35f83872021-11-25T06:09:24ZmiR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma.1932-620310.1371/journal.pone.0101899https://doaj.org/article/959f3298dafd4a1e9d1cc38ea35f83872014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25003366/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>High miR-141 and miR-200c expression are associated with shorter OS in NSCLC patients with adenocarcinoma through MET and angiogenesis.Rut TejeroAlfons NavarroMarc CampayoNuria ViñolasRamon M MarradesAnna CordeiroMarc Ruíz-MartínezSandra SantasusagnaLaureano MolinsJosep RamirezMariano MonzóPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e101899 (2014) |
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Medicine R Science Q Rut Tejero Alfons Navarro Marc Campayo Nuria Viñolas Ramon M Marrades Anna Cordeiro Marc Ruíz-Martínez Sandra Santasusagna Laureano Molins Josep Ramirez Mariano Monzó miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma. |
| description |
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>High miR-141 and miR-200c expression are associated with shorter OS in NSCLC patients with adenocarcinoma through MET and angiogenesis. |
| format |
article |
| author |
Rut Tejero Alfons Navarro Marc Campayo Nuria Viñolas Ramon M Marrades Anna Cordeiro Marc Ruíz-Martínez Sandra Santasusagna Laureano Molins Josep Ramirez Mariano Monzó |
| author_facet |
Rut Tejero Alfons Navarro Marc Campayo Nuria Viñolas Ramon M Marrades Anna Cordeiro Marc Ruíz-Martínez Sandra Santasusagna Laureano Molins Josep Ramirez Mariano Monzó |
| author_sort |
Rut Tejero |
| title |
miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma. |
| title_short |
miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma. |
| title_full |
miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma. |
| title_fullStr |
miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma. |
| title_full_unstemmed |
miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma. |
| title_sort |
mir-141 and mir-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/959f3298dafd4a1e9d1cc38ea35f8387 |
| work_keys_str_mv |
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