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Updated: Aug 28, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
FGFR1-4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer
Joanna Moes-Sosnowska1, Monika Skupinska2, Urszula Lechowicz1
1Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland.
Abstract:
While fibroblast growth factor receptors (FGFRs) are involved in several biological pathways and FGFR inhibitors may be useful in the treatment of squamous non-small cell lung cancer (Sq-NSCLC), FGFR aberrations are not well characterized in Sq-NSCLC. We comprehensively evaluated FGFR expression, fusions, and variants in 40 fresh-frozen primary Sq-NSCLC (stage IA3−IV) samples and tumor-adjacent normal tissues using real-time PCR and next-generation sequencing (NGS). Protein expression of FGFR1−3 and amplification of FGFR1 were also analyzed. FGFR1 and FGFR4 median gene expression was significantly (p < 0.001) decreased in tumors compared with normal tissue. Increased FGFR3 expression enhanced the recurrence risk (hazard ratio 4.72, p = 0.029), while high FGFR4 expression was associated with lymph node metastasis (p = 0.036). Enhanced FGFR1 gene expression was correlated with FGFR1 protein overexpression (r = 0.75, p = 0.0003), but not with FGFR1 amplification. NGS revealed known pathogenic FGFR2,3 variants, an FGFR3::TACC3 fusion, and a novel TACC1::FGFR1 fusion together with FGFR1,2 variants of uncertain significance not previously reported in Sq-NSCLC. These findings expand our knowledge of the Sq-NSCLC molecular background and show that combining different methods increases the rate of FGFR aberrations detection, which may improve patient selection for FGFRi treatment.
Insights
Fibroblast growth factor receptor (FGFR) aberrations in squamous non-small cell lung cancer (Sq-NSCLC) were characterized using multiple methods. This study identified novel FGFR fusions and variants, improving detection for targeted FGFR inhibitor therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Fibroblast growth factor receptors (FGFRs) play roles in various biological pathways.
- FGFR inhibitors show potential for treating squamous non-small cell lung cancer (Sq-NSCLC).
- FGFR aberrations are not fully understood in Sq-NSCLC.
Purpose of the Study:
- To comprehensively evaluate FGFR expression, fusions, and variants in Sq-NSCLC.
- To correlate FGFR alterations with clinical outcomes.
- To assess the utility of combined detection methods for FGFR aberrations.
Main Methods:
- Analysis of 40 fresh-frozen primary Sq-NSCLC samples and adjacent normal tissues.
- Real-time PCR and next-generation sequencing (NGS) for gene expression, fusions, and variants.
- Analysis of FGFR1-3 protein expression and FGFR1 amplification.
Main Results:
- FGFR1 and FGFR4 gene expression were significantly decreased in tumors versus normal tissue.
- Increased FGFR3 expression correlated with higher recurrence risk; high FGFR4 expression linked to lymph node metastasis.
- NGS identified known pathogenic variants, FGFR3::TACC3 fusion, a novel TACC1::FGFR1 fusion, and previously unreported FGFR1,2 variants.
Conclusions:
- This study expands the understanding of the Sq-NSCLC molecular landscape.
- Combining multiple detection methods enhances the identification rate of FGFR aberrations.
- Improved detection of FGFR aberrations can aid in patient selection for FGFR inhibitor treatments.
