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Fibroblast Growth Factor Receptor 1 and Related Ligands in Small-Cell Lung Cancer

Liping Zhang1, Hui Yu, Andrzej Badzio

  • 1*Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Institute, Shanghai, People's Republic of China; †Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; ‡Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland; §Institute of Pathology, University Hospital Cologne, Medical Centre, Cologne, Germany; ‖Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado; ¶Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; and #Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Institute, Shanghai, People's Republic of China.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
|May 29, 2015
PubMed
Abstract

Insights

A subset of small-cell lung cancer (SCLC) shows activated fibroblast growth factor (FGF)/FGFR1 pathways. FGFR1 expression correlates with mRNA levels and gene copy number, suggesting potential for FGFR1 inhibitor therapy in SCLC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Small-cell lung cancer (SCLC) represents 15% of lung cancers and has limited targeted therapy options.
  • Fibroblast growth factor (FGF) signaling, involving FGF2 and FGF9, is implicated in non-small-cell lung cancer progression.
  • Investigating fibroblast growth factor receptor 1 (FGFR1) and its ligands in SCLC is crucial for identifying novel therapeutic targets.

Purpose of the Study:

  • To evaluate the expression of FGFR1 and its ligands (FGF2, FGF9) in primary SCLC samples.
  • To determine the correlation between FGFR1 expression, mRNA levels, and gene copy number.
  • To assess the potential of targeting the FGF/FGFR1 pathway in SCLC.

Main Methods:

  • Analysis of FGFR1 protein, mRNA, and gene copy number in 90 primary SCLC tumors using immunohistochemistry (IHC) and in situ hybridization.
  • Assessment of FGF2 and FGF9 protein and mRNA expression via IHC and in situ hybridization.
  • Evaluation of FGFR1 protein expression in a separate cohort of 24 SCLC biopsy samples with known FGFR1 amplification.

Main Results:

  • FGFR1 protein expression significantly correlated with FGFR1 mRNA levels (p < 0.0001) and gene copy number (p = 0.03).
  • FGFR1 mRNA positivity was observed in 19.7% of cases and correlated with FGF2 and FGF9 mRNA and protein levels.
  • In cases with FGFR1 amplification, 73.9% showed positive FGFR1 protein expression.

Conclusions:

  • A subset of SCLC exhibits potentially activated FGF/FGFR1 signaling pathways.
  • FGFR1 protein expression is linked to its mRNA levels and gene amplification.
  • Combined analysis of FGFR1 and ligand expression may guide patient selection for FGFR1 inhibitor therapies in SCLC.

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