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urn:hdl:2445/130991 Clinical significance of long non-coding RNA HOTTIP in early-stage non-small-cell lung cancer 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 Càncer de pulmó RNA Lung cancer RNA 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. 2019-03-27T18:41:54Z 2019-03-27T18:41:54Z 2019-02-28 2019-03-27T18:41:54Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1186/s12890-019-0816-8 BMC Pulmonary Medicine, 2019, vol. 19, num. 1, p. 55-63 https://doi.org/10.1186/s12890-019-0816-8 cc-by (c) Navarro Ponz, Alfons et al., 2019 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess BioMed Central Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)