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. 2013 May;34(5):1031-8.
doi: 10.1093/carcin/bgt022. Epub 2013 Jan 24.

DICER1, DROSHA and miRNAs in patients with non-small cell lung cancer: implications for outcomes and histologic classification

C Vanesa Díaz-García  1 , Alba Agudo-López, Carlos Pérez, José A López-Martín, J Luis Rodríguez-Peralto, Javier de Castro, Ana Cortijo, Miriam Martínez-Villanueva, Lara Iglesias, Rocío García-Carbonero, Juan A Fresno Vara, Angelo Gámez-Pozo, José Palacios, Hernán Cortés-Funes, Luis Paz-Ares, M Teresa Agulló-Ortuño
Affiliations

DICER1, DROSHA and miRNAs in patients with non-small cell lung cancer: implications for outcomes and histologic classification

C Vanesa Díaz-García et al. Carcinogenesis. 2013 May.

Abstract

The clinical and functional significance of RNA-interference machinery in lung cancer is poorly understood. Besides, microRNAs (miRNA) have the potential to serve both as biomarkers and therapeutic agents, by personalizing diagnosis and therapy. In this study, we investigated whether the expression levels of DICER1 and DROSHA, components of the RNA-interference machinery, can predict survival, and whether the miRNA expression profiles can differentiate histologic subtypes in non-small cell lung cancer (NSCLC). Levels of DICER1, DROSHA and five different miRNAs were measured in NSCLC specimens (N = 115) by qRT-PCR assay and correlated with clinical outcomes. Low expression of DROSHA was associated with an increased median survival (154.2 versus 39.8 months, P = 0.016). Also, high DROSHA expression was associated with decreased median survival in the following subgroups: adenocarcinoma (P = 0.011), grade III tumors (P = 0.038) and low-stage patients (P = 0.014). In multivariate analyses, we found two independent predictors of reduced disease-specific survival: high DROSHA expression [hazards ratio = 2.24; P = 0.04] and advanced tumor stage (hazards ratio = 1.29, P = 0.02). In general, the overall tumor miRNA expression was downregulated in our cohort compared with normal tissues. Expression levels of hsa-let-7a (P = 0.005) and miR-16 (P = 0.003) miRNA were significantly higher in squamous cell carcinoma than in adenocarcinoma samples. This study supports the value of the expression profiling of the components of the miRNA-processing machinery in the prognosis of NSCLC patients, especially DROSHA expression levels. In addition, differential expression of miRNAs, such as hsa-let-7a and miR-16 may be helpful tools in the histologic subclassification of NSCLC.

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