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Vol. 56. Issue 10.
Pages 630-636 (October 2020)
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Vol. 56. Issue 10.
Pages 630-636 (October 2020)
Original Article
Long Non-Coding RNA NANCI/NKX2-1 Duplex Impacts Prognosis in Stage I Non-Small-Cell Lung Cancer
La combinación de NANCI/NKX2-1 de ARN no codificante de cadena larga afecta al pronóstico del cáncer de pulmón de células no pequeñas en estadio i
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Jorge Moisésa,f,1, Alfons Navarrob,1, Joan Josep Castellanob, Nuria Viñolasc, Laureano Molinsd, Jordi Canalsb, Bing Hanb, Jara Martínb, José Ramireze,f, Gerard Frigolae, Ramón María Marradesa,f,2, Mariano Monzób,2,
Corresponding author
mmonzo@ub.edu

Corresponding author.
a Department of Pneumology, Institut Clínic Respiratori (ICR), Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
b Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain
c Department of Medical Oncology, Institut Clínic de Malalties Hematològicas i Oncològiques (ICMHO), Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
d Department of Thoracic Surgery, Institut Clínic Respiratori (ICR), Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
e Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
f CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain
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Table 1. Main patient characteristics, univariate P-values (log-rank test) for disease-free survival (DFS) and overall survival (OS) and the mean±standard deviation (SD) of NANCI expression for each clinical characteristic compared by t-test or ANOVA test.
Table 2. Multivariate analysis for DFS and OS.
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Abstract
Background

NANCI, an intergenic long non-coding RNA (lncRNA) is essential for buffering NKX2-1 expression during embryonic development and in adult tissue. We analyzed NANCI and NKX2-1 in human lung embryonic samples and adult lung tissues and evaluated their potential as prognostic markers in stage I non-small cell lung cancer (NSCLC).

Methods and results

NANCI and NKX2-1 expression was assessed by TaqMan assays in 18 human embryonic samples from 8 to 13 weeks, 59 non-tumoral (NT) lung tissue samples, and 98 stage I NSCLC tumor samples. NANCI and NKX2-1 expression in embryonic and NSCLC samples were downregulated in comparison to adult NT tissue. Patients with low expression of NANCI had shorter disease-free survival (DFS) and overall survival (OS) than those with high levels (47.6 vs 69.3 months, P=0.032 and 57.7 vs 77.6 months, P=0.021, respectively). When the expression levels of NANCI and NKX2-1 were evaluated in combination, four groups were identified (high NANCI/high NKX2-1, low NANCI/high NKX2-1, high NANCI/low NKX2-1 and low NANCI/low NKX2-1) with differential impact on DFS (P=0.042) and OS (P=0.024). Interestingly, the high NANCI/high NKX2-1 duplex group had longer DFS and OS than the other three groups (71.25 vs 46.3 months, P=0.009 and 81.3 vs 56.1 months, P=0.004, respectively). In the multivariate analysis, the high NANCI/high NKX2-1 duplex was identified as an independent prognostic factor for longer DFS (HR 0.346, 95% CI, 0.169–0.709; P=0.004) and OS (HR 0.309, 95% CI, 0.121–0.786; P=0.014).

Conclusions

NANCI and the NANCI-NKX2-1 duplex impacts prognosis in stage I NSCLC patients.

Keywords:
NANCI
NKX2-1
LncRNA
NSCLC
Early-stage
Overall survival
Disease-free survival
Lung development
Resumen
Contexto global

NANCI, un ARN intergénico largo no codificante (lncRNA) es esencial para regular la expresión de NKX2-1 durante el desarrollo embrionario y en el tejido adulto. Analizamos la expresión de NANCI y NKX2-1 en muestras embrionarias de pulmón humano y tejidos pulmonares adultos, y evaluamos su potencial como marcadores pronósticos en el cáncer de pulmón de células no pequeñas (CPCNP) en estadio i.

Métodos y resultados

La expresión de NANCI y NKX2-1 se evaluó mediante ensayos TaqMan® en 18 muestras embrionarias humanas de 8 a 13 semanas, 59 muestras de tejido pulmonar no tumoral (NT) y 98 muestras de tumor de CPCNP en estadio i. La expresión de NANCI y NKX2-1 en muestras embrionarias y NSCLC se encontraba reducida en comparación con el tejido NT adulto. Los pacientes con baja expresión de NANCI tuvieron una supervivencia libre de enfermedad (SLE) y una supervivencia general (SG) más cortas que aquellos con niveles altos (47,6 frente a 69,3 meses; p=0,032 y 57,7 frente a 77,6 meses; p=0,021, respectivamente). Cuando se evaluaron los niveles de expresión de NANCI y NKX2-1 combinados se identificaron 4 grupos (NANCI alto/NKX2-1 alto, NANCI bajo/NKX2-1 alto, NANCI alto/NKX2-1 bajo y NANCI bajo/NKX2-1 bajo) con impacto variable en la SLE (p=0,042) y la SG (p=0,024). Curiosamente, la combinación de NANCI alto/NKX2-1 alto presentó unas SLE y SG más largas que los otros 3 grupos (71,25 frente a 46,3 meses; p=0,009 y 81,3 frente a 56,1 meses; p=0,004, respectivamente). En el análisis multivariante, la combinación de NANCI alto/NKX2-1 alto se identificó como un factor de pronóstico independiente para una SLE más larga (HR: 0,346; IC 95%: 0,169-0,709; p=0,004), al igual que la SG (HR: 0,309; IC 95%: 0,121-0,786; p=0,014).

Conclusiones

NANCI y la combinación de NANCI-NKX2-1 afecta al pronóstico de los pacientes con CPCNP en estadio i.

Palabras clave:
NANCI
NKX2-1
LncRNA
CPCNP
Estadios iniciales
Supervivencia general
Supervivencia libre de enfermedad
Desarrollo pulmonar

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