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Prognostic value of dual-specificity phosphatase 6 expression in non-small cell lung cancer

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Tumor Biology

Abstract

Dual-specificity phosphatase 6 (DUSP6/MKP-3) is a mitogen-activated protein kinase phosphatase that regulates extracellular signal-regulated kinases (ERKs) activity via feedback mechanisms, with an increasingly recognized role in tumour biology. The aim of this study was to explore the role of DUSP6 expression in the prognosis of human non-small cell lung cancer (NSCLC). DUSP6 expression levels were evaluated by real-time quantitative reverse transcription polymerase chain reaction (PCR) in 60 NSCLC samples from patients who underwent pulmonary resection at 12 de Octubre University Hospital. We performed a statistical analysis to investigate the correlation of DUSP6 expression and the clinical outcomes. We found that 66.7 % of the tumour samples show the downregulation of DUSP6 at the messenger RNA (mRNA) levels compared to benign epithelial lung tissues and 55 % of them show at least twofold downregulation of DUSP6 gene expression. Patients were classified into three groups according to their DUSP6 expression levels and those with very low levels (at least twofold downregulation) had the worst outcomes. Using the value of twice below the mean value in benign epithelial lung tissue as a cutoff, the overall survival of patients with very low DUSP6 levels was significantly lower than that in the rest of patients (31.9 ± 18.8 months vs. not reached, P = 0.049). This was most pronounced in adenocarcinoma histology and high-stage tumour samples. Our results suggest that DUSP6 gene expression in tumour samples may be a prognostic marker in NSCLC.

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Acknowledgments

This work was partially supported by Fundación Médica Mutua Madrileña (Madrid, Spain) grant 2008/107 and by Comunidad de Madrid (Biomedicina S2010/BMD-2326, Inmunothercan-CM). VD-G is supported by Fundación Mutua Madrileña 2010/018, AA-L by Red Temática de Investigación Corporativa del Cáncer (RTICC, ISCIII, Spain), CP by Ministerio de Sanidad y Política Social (TRA-151, Spain) and MTA-O by Instituto de Salud Carlos III (Programa Post-Formación Sanitaria Especializada FIS-CM 06/00231). We thank Dr. Juan Carlos Rubio (Genomic Department, Instituto de Investigación Hospital 12 de Octubre, Madrid) and Alberto Muro (Translational Oncology, Instituto de Investigación Hospital 12 de Octubre, Madrid) for their technical support.

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Authors and Affiliations

  1. Laboratory of Translational Oncology, Instituto de Investigación Hospital 12 de Octubre (i+12), Avda de Córdoba S/N, 28041, Madrid, Spain

    C. Vanesa Díaz-García, Alba Agudo-López, Carlos Pérez, Elena Prieto-García, José L. Rodríguez-Peralto, Hernán Cortés-Funes, José A. López-Martín & M. Teresa Agulló-Ortuño

  2. Oncology Department, Hospital Universitario 12 de Octubre, Avda de Córdoba S/N, 28041, Madrid, Spain

    Lara Iglesias, Santiago Ponce, Analia Rodríguez Garzotto, Hernán Cortés-Funes & José A. López-Martín

  3. Pathology Department, Hospital Universitario 12 de Octubre, Avda de Córdoba S/N, 28041, Madrid, Spain

    José L. Rodríguez-Peralto

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  1. C. Vanesa Díaz-García
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  2. Alba Agudo-López
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Correspondence to M. Teresa Agulló-Ortuño.

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Díaz-García, C.V., Agudo-López, A., Pérez, C. et al. Prognostic value of dual-specificity phosphatase 6 expression in non-small cell lung cancer. Tumor Biol. 36, 1199–1206 (2015). https://doi.org/10.1007/s13277-014-2729-8

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