NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer

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...

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Autores: 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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/122905
Acceso en línea:https://hdl.handle.net/2445/122905
Access Level:acceso abierto
Palabra clave:Càncer de pulmó
Marcadors tumorals
Lung cancer
Tumor markers
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spelling NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancerMoisés, JorgeNavarro Ponz, AlfonsSantasusagna, SandraViñolas Segarra, NúriaMolins López-Rodó, LaureanoRamirez, JoséOsorio, JeissonSaco, AdelaCastellano, Joan JosepMuñoz García, CarmenMorales, SaraMonzó Planella, MarianoMarrades Sicart, Ramon Ma.Càncer de pulmóMarcadors tumoralsLung cancerTumor markersBACKGROUND: 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.BioMed Central2018201820172018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/122905Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1186/s12890-017-0542-zBMC Pulmonary Medicine, 2017, vol. 17, num. 197https://doi.org/10.1186/s12890-017-0542-zcc-by (c) Moisés, Jorge et al., 2017http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1229052026-05-29T05:05:01Z
dc.title.none.fl_str_mv NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer
title NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer
spellingShingle NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer
Moisés, Jorge
Càncer de pulmó
Marcadors tumorals
Lung cancer
Tumor markers
title_short NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer
title_full NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer
title_fullStr NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer
title_full_unstemmed NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer
title_sort NKX2-1 expression as a prognostic marker in early-stage non-small-cell lung cancer
dc.creator.none.fl_str_mv 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.
author Moisés, Jorge
author_facet 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.
author_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de pulmó
Marcadors tumorals
Lung cancer
Tumor markers
topic Càncer de pulmó
Marcadors tumorals
Lung cancer
Tumor markers
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/122905
url https://hdl.handle.net/2445/122905
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12890-017-0542-z
BMC Pulmonary Medicine, 2017, vol. 17, num. 197
https://doi.org/10.1186/s12890-017-0542-z
dc.rights.none.fl_str_mv cc-by (c) Moisés, Jorge et al., 2017
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Moisés, Jorge et al., 2017
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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