FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer
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, fu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10506 |
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| author | Joanna Moes-Sosnowska Monika Skupinska Urszula Lechowicz Ewa Szczepulska-Wojcik Paulina Skronska Adriana Rozy Aneta Stepniewska Renata Langfort Piotr Rudzinski Tadeusz Orlowski Delfina Popiel Aleksandra Stanczak Maciej Wieczorek Joanna Chorostowska-Wynimko |
| author_facet | Joanna Moes-Sosnowska Monika Skupinska Urszula Lechowicz Ewa Szczepulska-Wojcik Paulina Skronska Adriana Rozy Aneta Stepniewska Renata Langfort Piotr Rudzinski Tadeusz Orlowski Delfina Popiel Aleksandra Stanczak Maciej Wieczorek Joanna Chorostowska-Wynimko |
| author_sort | Joanna Moes-Sosnowska |
| collection | DOAJ |
| description | 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 <i>FGFR1</i> were also analyzed. <i>FGFR1</i> and <i>FGFR4</i> median gene expression was significantly (<i>p</i> < 0.001) decreased in tumors compared with normal tissue. Increased <i>FGFR3</i> expression enhanced the recurrence risk (hazard ratio 4.72, <i>p</i> = 0.029), while high <i>FGFR4</i> expression was associated with lymph node metastasis (<i>p</i> = 0.036). Enhanced <i>FGFR1</i> gene expression was correlated with FGFR1 protein overexpression (r = 0.75, <i>p</i> = 0.0003), but not with <i>FGFR1</i> amplification. NGS revealed known pathogenic <i>FGFR2,3</i> variants, an FGFR3::TACC3 fusion, and a novel TACC1::FGFR1 fusion together with <i>FGFR1,2</i> 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. |
| first_indexed | 2024-03-09T23:46:11Z |
| format | Article |
| id | doaj.art-d7e15ec635194835b16d7385efbb929d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:46:11Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d7e15ec635194835b16d7385efbb929d2023-11-23T16:42:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181050610.3390/ijms231810506FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung CancerJoanna Moes-Sosnowska0Monika Skupinska1Urszula Lechowicz2Ewa Szczepulska-Wojcik3Paulina Skronska4Adriana Rozy5Aneta Stepniewska6Renata Langfort7Piotr Rudzinski8Tadeusz Orlowski9Delfina Popiel10Aleksandra Stanczak11Maciej Wieczorek12Joanna Chorostowska-Wynimko13Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandPreclinical Development Department, Celon Pharma S.A, Research & Development Centre, 05-152 Kazun Nowy, PolandDepartment of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandDepartment of Pathology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandDepartment of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandDepartment of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandDepartment of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandDepartment of Pathology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandDepartment of Surgery, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandDepartment of Surgery, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandPreclinical Development Department, Celon Pharma S.A, Research & Development Centre, 05-152 Kazun Nowy, PolandClinical Development Department, Celon Pharma S.A., Research & Development Centre, 05-152 Kazun Nowy, PolandPreclinical Development Department, Celon Pharma S.A, Research & Development Centre, 05-152 Kazun Nowy, PolandDepartment of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, PolandWhile 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 <i>FGFR1</i> were also analyzed. <i>FGFR1</i> and <i>FGFR4</i> median gene expression was significantly (<i>p</i> < 0.001) decreased in tumors compared with normal tissue. Increased <i>FGFR3</i> expression enhanced the recurrence risk (hazard ratio 4.72, <i>p</i> = 0.029), while high <i>FGFR4</i> expression was associated with lymph node metastasis (<i>p</i> = 0.036). Enhanced <i>FGFR1</i> gene expression was correlated with FGFR1 protein overexpression (r = 0.75, <i>p</i> = 0.0003), but not with <i>FGFR1</i> amplification. NGS revealed known pathogenic <i>FGFR2,3</i> variants, an FGFR3::TACC3 fusion, and a novel TACC1::FGFR1 fusion together with <i>FGFR1,2</i> 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.https://www.mdpi.com/1422-0067/23/18/10506fibroblast growth factor receptorFGFR1FGFR2FGFR3FGFR4gene expression |
| spellingShingle | Joanna Moes-Sosnowska Monika Skupinska Urszula Lechowicz Ewa Szczepulska-Wojcik Paulina Skronska Adriana Rozy Aneta Stepniewska Renata Langfort Piotr Rudzinski Tadeusz Orlowski Delfina Popiel Aleksandra Stanczak Maciej Wieczorek Joanna Chorostowska-Wynimko FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer International Journal of Molecular Sciences fibroblast growth factor receptor FGFR1 FGFR2 FGFR3 FGFR4 gene expression |
| title | FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer |
| title_full | FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer |
| title_fullStr | FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer |
| title_full_unstemmed | FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer |
| title_short | FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer |
| title_sort | fgfr1 4 rna based gene alteration and expression analysis in squamous non small cell lung cancer |
| topic | fibroblast growth factor receptor FGFR1 FGFR2 FGFR3 FGFR4 gene expression |
| url | https://www.mdpi.com/1422-0067/23/18/10506 |
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