To access the full text documents, please follow this link: http://hdl.handle.net/2445/122905

Title:	NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer
Author:	Moisés, Jorge; Navarro Ponz, Alfons; Santasusagna, Sandra; Viñolas Segarra, Núria; Molins López-Rodó, Laureano; Ramirez, José; Osorio, Jeisson; Saco, Adela; Castellano, Joan Josep; Muñoz García, Carmen; Morales, Sara; Monzó Planella, Mariano; Marrades Sicart, Ramon Ma.
Notes:	BACKGROUND: NKX2-1, a key molecule in lung development, is highly expressed in non-small cell lung cancer (NSCLC), particularly in lung adenocarcinoma (ADK), where it is a diagnostic marker. Studies of the prognostic role of NKX2-1 in NSCLC have reported contradictory findings. Two microRNAs (miRNAs) have been associated with NKX2-1: miR-365, which targets NKX2-1; and miR-33a, which is downstream of NKX2-1. We have examined the effect of NKX2-1, miR-365 and miR-33a on survival in a cohort of early-stage NSCLC patients and in sub-groups of patients classified according to the mutational status of TP53, KRAS, and EGFR. METHODS: mRNA and miRNA expression was determined using TaqMan assays in 110 early-stage NSCLC patients. TP53, KRAS, and EGFR mutations were assessed by Sanger sequencing. RESULTS: NKX2-1 expression was upregulated in never-smokers (P = 0.017), ADK (P < 0.0001) and patients with wild-type TP53 (P = 0.001). A negative correlation between NKX2-1 and miR-365 expression was found (ρ = -0.287; P = 0.003) but there was no correlation between NKX2-1 and miR-33a expression. Overall survival (OS) was longer in patients with high expression of NKX2-1 than in those with low expression (80.8 vs 61.2 months (P = 0.035), while a trend towards longer OS was observed in patients with low miR-365 levels (P = 0.07). The impact of NKX2-1 on OS and DFS was higher in patients with neither TP53 nor KRAS mutations. Higher expression of NKX2-1 was related to higher OS (77.6 vs 54 months; P = 0.017) and DFS (74.6 vs 57.7 months; P = 0.006) compared to low expression. The association between NKX2-1 and OS and DFS was strengthened when the analysis was limited to patients with stage I disease (P = 0.005 and P=0.003 respectively). CONCLUSIONS: NKX2-1 expression impacts prognosis in early-stage NSCLC patients, particularly in those with neither TP53 nor KRAS mutations.
Subject(s):	-Càncer de pulmó -Marcadors tumorals -Lung cancer -Tumor markers
Rights:	cc-by (c) Moisés, Jorge et al., 2017 http://creativecommons.org/licenses/by/3.0/es
Document type:	Article Article - Published version
Published by:	BioMed Central
Share:

Show full item record