1563P - The oncogenic role of FGFR1 depends on the molecular context

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Presenter Alvaro Quintanal
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors A. Quintanal1, I. Ferrer1, L. Ojeda-Márquez1, Á. Marrugal1, R. Suarez1, L. García-Redondo1, A. Carnero2, L. Paz-Ares3, S. Molina-Pinelo1
  • 1H120-cnio Lung Cancer Clinical Research Unit, CNIO- Spanish National Cancer Center, 28029 - Madrid/ES
  • 2Molecular Oncology Laboratory, IBIS, 41013 - Sevilla/ES
  • 3Medical Oncology, Hospital Universitario Doce de Octubre, 28041 - Madrid/ES

Abstract

Background

The FGFR protein family has been extensively related to oncogenesis in several types of tumors, including lung cancer. In squamous cell lung carcinoma, 20% of patients harbour FGFR1 amplification. However, its role in lung cancer has not yet been thoroughly described.

Methods

Several lung cell lines with different genetic backgrounds were transfected with plasmids to either overexpress or silence FGFR1. In these models, several tumorigenic abilities were tested in vitro and in vivo. Besides, mRNA from formalin-fixed paraffin-embedded tissue of a cohort of lung cancer patients was extracted and FGFR1 expression levels, as well as other histology-specific differentially expressed genes, were measured and related to clinical characteristics.

Results

FGFR1 increases oncogenic properties in SCC cell lines, but exerts the opposite effects in several lung ADC cell lines. This behaviour is a consequence of differentially expressed genes between these two histologies in the cell lines under study. According to this, analysis of FGFR1 mRNA expression, along with the above mentioned differentially expressed genes, in a cohort of lung cancer patients, reinforced our in vitro results. In this patient cohort, high FGFR1 mRNA expression was associated to a shorter overall survival (OS) and progression free survival (PFS) in lung SCC patients. However, a trend for longer OS was observed for the ADC patients with higher FGFR1 mRNA expression.

Conclusions

We provide evidence that FGFR1 oncogenic role is dependent of its molecular context, resulting in a differential role for this gene in tumorigenesis. This involves a differential prognostic role of this gene in the two main lung cancer histologies. The characterization of this molecular context may be of interest in order to decide the suitability for a patient to receive anti-FGFR therapy.

Clinical trial identification

Legal entity responsible for the study

CNIO

Funding

ISCIII

Disclosure

All authors have declared no conflicts of interest.