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.
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.
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.
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.
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All authors have declared no conflicts of interest.