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Title: The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer
Author: Navarro Ponz, Alfons
Tejero Villalba, Rut
Viñolas Segarra, Núria
Cordeiro Santanach, Anna
Marrades Sicart, Ramon Ma.
Fuster, Dolors
Caritg, Oriol
Moises, Jorge
Muñoz García, Carmen
Molins López-Rodó, Laureano
Ramírez Ruz, J. (José)
Monzó Planella, Mariano
Keywords: Càncer de pulmó
Micro RNAs
Lung cancer
Issue Date: 23-Jan-2015
Publisher: Impact Journals
Abstract: The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower levels of PIWIL4 had shorter TTR (p = 0.048) and OS (p = 0.033). In the multivariate analysis, PIWIL1 expression emerged as an independent prognostic marker. Using 5-Aza-dC treatment and bisulfite sequencing, we observed that PIWIL1 expression could be regulated in part by methylation. Finally, an in silico study identified a stem-cell expression signature associated with PIWIL1 expression.
Note: Reproducció del document publicat a:
It is part of: Oncotarget, 2015, vol. 6, num. 31, p. 31544-31556
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)

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