1284P - HOXA-related long non-coding RNAs impact prognosis in early stage NSCLC patients

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Non-Small-Cell Lung Cancer, Early Stage
Lung and other Thoracic Tumours
Translational Research
Presenter Alfons Navarro
Citation Annals of Oncology (2017) 28 (suppl_5): v453-v456. 10.1093/annonc/mdx381
Authors A. Navarro1, S. Santasusagna1, N. Vinolas Segarra2, J.J. Castellano1, J. Moises3, S. Morales1, J. Canals1, C. Muñoz1, J. Ramírez4, R.M. Marrades3, L. Molins5, M. Monzo1
  • 1Molecular Oncology And Embryology Laboratory, Human Anatomy Unit, University of Barcelona, 08036 - Barcelona/ES
  • 2Medical Oncology, Hospital Clinic y Provincial de Barcelona, 8036 - Barcelona/ES
  • 3Pneumology, Hospital Clinic y Provincial de Barcelona, 8036 - Barcelona/ES
  • 4Pathology, Hospital Clinic y Provincial de Barcelona, 8036 - Barcelona/ES
  • 5Thoracic Surgery, Hospital Clinic y Provincial de Barcelona, 8036 - Barcelona/ES

Abstract

Background

HOX genes, grouped in four clusters in humans (HOXA-D), encode for transcription factors that are master regulators of embryonic development and oncogenesis. HOXA cluster, located in chromosome 7, play a critical role in the patterning of tissues with mesodermal components such as lungs. Long non-coding RNAs (lncRNAs) are especially abundant in the HOXA cluster (HOXA10-AS, HOXAS2, HOXAS3, HOXA11-AS, HOTAIRM1 and HOTTIP). We aimed to evaluate the prognostic role of HOXA-related lncRNAs in early stage non-small cell lung cancer (NSCLC).

Methods

100 early stage NSCLC patients resected in our center from June 2007 to November 2013 were studied. Patient characteristics: median age, 65 (32-84); 78% males; 74% stage I; 56% ADK; 23% received adjuvant treatment. With a mean follow-up of 28.7 months, 31% relapsed. As validation data set 200 NSCLC patients from TCGA Research Network were used (RNAseq data). Only stage I-II TCGA samples without prior malignancy or synchronous cancer that not received neoadjuvant treatment were included. Statistical analysis was performed using R and TANRIC.

Results

HOTTIP and HOXA11AS impacted prognosis in our cohort of patients. HOTTIP was expressed in all samples and 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). HOTTIP was overexpressed in SCC (p = 0.007) and in smokers (p = 0.018). HOXA11AS was expressed only in 9% of patients but the patients expressing HOXA11AS had shorter TTR (73.5 vs 32 months; p = 0.002). In the multivariate analysis HOXA11AS emerged as an independent prognostic marker for TTR (OR: 3.13, 95%CI: 1.3-7.3; p = 0.009), while HOTTIP (OR: 2.357, 95%CI: 1.1-5.2; p = 0.036) and age>65 (p = 0.022) for OS. In the validation data set HOXA11AS was validated as prognostic marker (p = 0.019). HOXA11AS expression correlated positively with development genes HOXA11, HOXA13, HOXA10, HOXA9, HOXA3, FOXD1, ZIC5 and miR-196b (HOXA cluster miRNA) and negatively with surfactant metabolism genes SFTPB and NAPSA or let-7a(p 

Conclusions

HOXA11AS expression in early stage NSCLC patients is a high-risk relapse marker.

Clinical trial identification

Legal entity responsible for the study

University of Barcelona, Barcelona, Spain

Funding

None

Disclosure

All authors have declared no conflicts of interest.