title: Prognostic value of dual-specificity phosphatase 6 expression in non-small cell lung cancer.
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.
authors.affiliation: Laboratory of Translational Oncology, Instituto de Investigación Hospital 12 de Octubre (i+12), Avda de Córdoba S/N, 28041, Madrid, Spain.
authors.forename: C Vanesa
authors.initials: CV
authors.lastname: Díaz-García
authors.forename: Alba
authors.initials: A
authors.lastname: Agudo-López
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez
authors.forename: Elena
authors.initials: E
authors.lastname: Prieto-García
authors.forename: Lara
authors.initials: L
authors.lastname: Iglesias
authors.forename: Santiago
authors.initials: S
authors.lastname: Ponce
authors.forename: Analia
authors.initials: A
authors.lastname: Rodríguez Garzotto
authors.forename: José L
authors.initials: JL
authors.lastname: Rodríguez-Peralto
authors.forename: Hernán
authors.initials: H
authors.lastname: Cortés-Funes
authors.forename: José A
authors.initials: JA
authors.lastname: López-Martín
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Agulló-Ortuño
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D054642:Dual Specificity Phosphatase 6 / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6