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Title: Clinical significance of long non-coding RNA HOTTIP in early-stage non-small-cell lung cancer
Author: Navarro Ponz, Alfons
Moisés, Jorge
Santasusagna, Sandra
Marrades Sicart, Ramon Ma.
Viñolas Segarra, Núria
Castellano, Joan Josep
Canals, Jordi
Muñoz García, Carmen
Ramirez, José
Molins López-Rodó, Laureano
Monzó Planella, Mariano
Keywords: Càncer de pulmó
Lung cancer
Issue Date: 28-Feb-2019
Publisher: BioMed Central
Abstract: Background HOTTIP, a long non-coding RNA located in the HOXA cluster, plays a role in the patterning of tissues with mesodermal components, including the lung. Overexpression of HOXA genes, including HOTTIP, has been associated with a more aggressive phenotype in several cancers. However, the prognostic impact of HOTTIP has not yet been explored in non-small-cell lung cancer (NSCLC). We have correlated HOTTIP expression with time to relapse (TTR) and overall survival (OS) in early-stage NSCLC patients. Methods Ninety-nine early-stage NSCLC patients who underwent surgical resection in our center from June 2007 to November 2013 were included in the study. Mean age was 66; 77.8% were males; 73.7% had stage I disease; and 55.5% had adenocarcinoma. A validation data set comprised stage I-II patients from The Cancer Genome Atlas (TCGA) Research Network. Results HOTTIP was expressed in all tumor samples and was overexpressed in squamous cell carcinoma (p = 0.007) and in smokers (p = 0.018). Patients with high levels of HOTTIP had shorter TTR (78.3 vs 58 months; p = 0.048) and shorter OS (81.2 vs 61 months; p = 0.023) than those with low levels. In the multivariate analysis, HOTTIP emerged as an independent prognostic marker for TTR (OR: 2.05, 95%CI: 1-4.2; p = 0.05), and for OS (OR: 2.31, 95%CI: 1.04-5.1; p = 0.04). HOTTIP was validated as a prognostic marker for OS in the TCGA adenocarcinoma cohort (p = 0.025). Moreover, we identified a 1203-mRNA and a 61-miRNA signature that correlated with HOTTIP expression. Conclusions The lncRNA HOTTIP can be considered a prognostic biomarker in early-stage NSCLC.
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It is part of: BMC Pulmonary Medicine, 2019, vol. 19, num. 1, p. 55-63
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ISSN: 1471-2466
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)

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