Abstract
Lifestyle factors, including smoking, have been linked to neoplastic diseases, and reports suggest an association between smoking and overexpression of FGFR (fibroblast growth factor receptor) in certain neoplasms. This study aims to assess the expression of FGFR3 and FGFR4 genes in patients with and without a history of smoking.
A total of 118 participants were recruited, including 83 Juvenile Nasopharyngeal Angiofibroma (JNA) patients and 35 healthy participants, the JNA patients were further stratified as smokers and nonsmokers. Total RNA was extracted from the blood & saliva sample by using TRIzol reagent, and quantified using a Nanodrop, and then subjected to gene expression analysis of FGFR3/4 using RT-PCR. Immunohistochemistry analysis was employed using fresh biopsies of JNA to validate the findings. All experiments were performed in triplicates and analysed using the Chi-Square test (P < 0.05). Smokers exhibited significantly lower total RNA concentrations across all sample types (P < 0.001). The study revealed significant upregulation of both FGFR3/4 genes in JNA patients (P < 0.05). Moreover, FGFR3 expression was significantly higher among smokers 66% (95% CI: 53–79%) compared to non-smokers 22% (95% CI: 18–26%). Immunohistochemistry analysis demonstrated moderate to strong staining intensity for FGFR3 among smokers. The study highlights the overexpression of FGFR3/4 genes in JNA patients, with a stronger association observed among smokers. Furthermore, medical reports indicated higher rates of recurrence and bleeding intensity among smokers. These findings emphasize the potential role of FGFR3 as a key molecular factor in JNA, particularly in the context of smoking.
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Data Availability
The data that support the findings of this study are available from the authors but restrictions apply to the availability of these data, which were used under license from the National Committee of Bioethics, King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia (Study number H-01-R059, IRB LOG number 20–0287, dated Aug 27, 2020) for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission from the National Committee of Bioethics, King Abdulaziz City for Science and Technology.
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Acknowledgements
Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2023R318), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Funding
This research was funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2023R318), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
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Conceptualization, Fatmah Ahmed Safhi; Data curation, Fatmah Ahmed Safhi, Tahani Al-Hazani, Areej Jalal, Manal Alduwish, Dalal Alshaya, Dalia Domiaty, Eman Abdullah Alshehri, Salha Alshamrani, Nouf Al-Ghamdi, Mashael Alotaibi and Maha Awaili; Formal analysis, Fatmah Ahmed Safhi, Tahani Al-Hazani, Areej Jalal, Manal Alduwish, Nawaf Almufareh, Eman Abdullah Alshehri, Salha Alshamrani, Mashael Alotaibi, Maha Awaili and Wedad Al-Qahtani; Funding acquisition, Fatmah Ahmed Safhi; Investigation, Fatmah Ahmed Safhi, Tahani Al-Hazani, Manal Alduwish, Nawaf Almufareh, Dalia Domiaty, Eman Abdullah Alshehri, Nouf Al-Ghamdi, Mashael Alotaibi, Maha Awaili and Wedad Al-Qahtani; Methodology, Tahani Al-Hazani, Areej Jalal, Manal Alduwish, Dalal Alshaya, Nawaf Almufareh, Dalia Domiaty, Eman Abdullah Alshehri, Salha Alshamrani, Nouf Al-Ghamdi, Mashael Alotaibi, Maha Awaili and Wedad Al-Qahtani; Project administration, Wedad Al-Qahtani; Resources, Fatmah Ahmed Safhi, Dalal Alshaya, Nawaf Almufareh, Salha Alshamrani, Mashael Alotaibi and Wedad Al-Qahtani; Software, Fatmah Ahmed Safhi, Tahani Al-Hazani, Areej Jalal, Manal Alduwish, Dalal Alshaya, Eman Abdullah Alshehri, Salha Alshamrani and Nouf Al-Ghamdi; Supervision, Wedad Al-Qahtani; Validation, Fatmah Ahmed Safhi, Tahani Al-Hazani, Areej Jalal, Dalal Alshaya, Nawaf Almufareh, Dalia Domiaty, Nouf Al-Ghamdi, Maha Awaili and Wedad Al-Qahtani; Visualization, Dalia Domiaty, Salha Alshamrani, Mashael Alotaibi, Maha Awaili and Wedad Al-Qahtani; Writing – original draft, Wedad Al-Qahtani; Writing – review & editing, Fatmah Ahmed Safhi, Tahani Al-Hazani, Areej Jalal, Manal Alduwish, Dalal Alshaya, Nawaf Almufareh, Dalia Domiaty, Eman Abdullah Alshehri, Salha Alshamrani, Nouf Al-Ghamdi, Mashael Alotaibi, Maha Awaili and Wedad Al-Qahtani.
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Highlights
1. The underlying cause and pathogenesis of JNA are not fully understood, although genetic, hormonal and lifestyle factors are reported to be associated with JNA.
2. Several biomarkers are being explored for targeted molecular therapies for JNA management, among which fibroblast growth factor receptors (FGFR) are widely researched.
3. FGF 3/4 promising to be powerful biomarkers and therapeutic targets for JNA tumor.
4. The association of JNA with smoking and FGFR expression among JNA patients with and without a history of smoking is not explored.
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Safhi, F.A., Al-Hazani, T.M.I., Jalal, A.S. et al. FGFR3 and FGFR4 overexpression in juvenile nasopharyngeal angiofibroma: impact of smoking history and implications for personalized management. J Appl Genetics 64, 749–758 (2023). https://doi.org/10.1007/s13353-023-00780-w
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DOI: https://doi.org/10.1007/s13353-023-00780-w