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01.12.2019 | Research article | Ausgabe 1/2019 Open Access

BMC Pulmonary Medicine 1/2019

Clinical significance of long non-coding RNA HOTTIP in early-stage non-small-cell lung cancer

BMC Pulmonary Medicine > Ausgabe 1/2019
Alfons Navarro, Jorge Moises, Sandra Santasusagna, Ramon M. Marrades, Nuria Viñolas, Joan J. Castellano, Jordi Canals, Carmen Muñoz, José Ramírez, Laureano Molins, Mariano Monzo
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12890-019-0816-8) contains supplementary material, which is available to authorized users.



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.


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.


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.


The lncRNA HOTTIP can be considered a prognostic biomarker in early-stage NSCLC.
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