Long Non-Coding RNA NANCI/NKX2-1 Duplex Impacts Prognosis in Stage I Non-Small-Cell Lung Cancer |
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| Institution: | 1. Department of Pneumology, Institut Clínic Respiratori (ICR), Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain;2. Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain;3. Department of Medical Oncology, Institut Clínic de Malalties Hematològicas i Oncològiques (ICMHO), Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain;4. Department of Thoracic Surgery, Institut Clínic Respiratori (ICR), Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain;5. Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain;6. CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain;1. Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Spain;2. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain;3. Grupo NeumoVigo I+i, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Servicio de Neumología, Hospital Álvaro Cunqueiro, Vigo, Pontevedra, Spain;4. Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain;5. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain;1. Servicio de Neumología, Hospital Clínico Universitario, INCLIVA, Valencia, Spain;2. UGCMQ de enfermedades respiratorias, Hospital Regional Universitario de Málaga, Málaga, Spain;3. Unidad Especializada en Tabaquismo, Hospital Clínico San Carlos, Madrid, Spain;1. Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain;2. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain;3. Fundación Jiménez Díaz, Hospital Universitario, Grupo Quirón, Madrid, Spain;4. Unidad especializada en Tabaquismo, Comunidad de Madrid, C.E. Modesto Lafuente, Madrid, Spain;1. Department of Respiratory Disease, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Naka-ku, Hiroshima, Japan;2. Department of Rheumatology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Naka-ku, Hiroshima, Japan;3. Department of Molecular and Internal Medicine, Institute of Biomedical & Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan;4. Ohashi Clinic, Naka-ku, Hiroshima, Japan;1. Servicio de Cirugía Torácica, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain;2. Servicio de Urgencias Generales, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain;3. Servicio de Epidemiología Clínica, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain |
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| Abstract: | BackgroundNANCI, 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 resultsNANCI 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).ConclusionsNANCI and the NANCI-NKX2-1 duplex impacts prognosis in stage I NSCLC patients. |
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| Keywords: | NANCI NKX2-1 LncRNA NSCLC Early-stage Overall survival Disease-free survival Lung development NANCI NKX2-1 LncRNA CPCNP Estadios iniciales Supervivencia general Supervivencia libre de enfermedad Desarrollo pulmonar |
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