Volume 31, Issue 146 (May & June 2023)                   J Adv Med Biomed Res 2023, 31(146): 230-237 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Behrouzi Pouya F, Saffari M, Muhammadnejad A, Monsef Shokri M, Shirkoohi R. A Study of Platelet-Derived Growth Factor A and Its Ligand among Patients with Glioblastoma and Astrocytoma in Imam Khomeini Hospital Complex, Tehran. J Adv Med Biomed Res 2023; 31 (146) :230-237
URL: http://journal.zums.ac.ir/article-1-6857-en.html
A Study of Platelet-Derived Growth Factor A and Its Ligand among Patients with Glioblastoma and Astrocytoma in Imam Khomeini Hospital Complex, Tehran
Fateme Behrouzi Pouya1 , Mojtaba Saffari2 , Ahad Muhammadnejad3 , Maryam Monsef Shokri4 , Reza Shirkoohi 5
1- Dept. of Biochemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
2- Dept. of Genetic, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
3- Dept. of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
4- International Sturgeon Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Rasht, Iran
5- Cancer Biology Research Center, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran , rshirkoohi@tums.ac.ir
Abstract:   (2769 Views)

Background and Objective: The platelet-derived growth factor receptor (PDGFR) signaling pathway has a vital function as a regulator of glioma development. PDGFRA alterations have been observed in a variety of cancers and have been important clinical targets for tyrosine kinase inhibitors like Imatinib. The aim of this study was to evaluate the role of PDGFRA and PDGFA in the pathogenesis of GBM and to determine whether the constitutive activation of PDGFRA is driven by gene mutations or protein expression.
Materials and Methods: PDGFRA-activating gene mutations (exons 12, 18) were assessed in a subset of 75 samples, of which 65 were GBM and 10 were pilocytic astrocytoma, using PCR followed by direct sequencing. PDGFA expression was evaluated by immunohistochemistry in a series of 20 cases including 15 cases of glioblastoma multiforme and 5 cases of pilocytic astrocytoma.
Results: No PDGFRA-activating mutations were found by Sanger sequencing. In addition, this study found polymorphism in PDGFRA exon 12, c.1701A> G, which was a silent mutation. Immunohistochemical analysis showed elevated PDGFA expression in 25% (5 out of 20) of glioma cases. PDGFA expression was not detected in any pilocytic astrocytoma; however, 33.33% (5 out of 15) of GBM samples showed increased PDGFA expression.
Conclusion: Consistent with previous studies, the findings of the present study underline the importance of PDGFA and PDGFRA alterations as a possible potential predictive biomarker and a therapeutic target in GBM. Further research is needed to better understand the underlying genetic mechanisms driving abnormal PDGFRA activity in gliomas.

Keywords: Glioblastoma, Imatinib, Mutations, PDGFRA, PDGFA, Receptor Tyrosine Kinase
Full-Text [PDF 680 kb]   (1688 Downloads) |   |   Full-Text (HTML)  (383 Views)  

✅ Consistent with previous studies, the findings of the present study underline the importance of PDGFA and PDGFRA alterations as a possible potential predictive biomarker and a therapeutic target in GBM. Further research is needed to better understand the underlying genetic mechanisms driving abnormal PDGFRA activity in gliomas.


Type of Study: Original Article | Subject: Medical Biology
Received: 2022/08/17 | Accepted: 2023/01/13 | Published: 2023/06/26
References
1. DeAngelis LM. Brain tumors. N Engl J Med. 2001; 344(2):114-23. [DOI:10.1056/NEJM200101113440207] [PMID]
2. Louis D, Ohgaki H, Wiestler O, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007. 114(2): 97-109. [DOI:10.1007/s00401-007-0243-4] [PMID] [PMCID]
3. Frank B Furnari, Tim Fenton , et al, Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007; 21(21): 2683-710. [DOI:10.1101/gad.1596707] [PMID]
4. Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013; 19(4): 764-72. [DOI:10.1158/1078-0432.CCR-12-3002] [PMID]
5. Dubrow R, Darefsky A. Demographic variation in incidence of adult glioma by subtype, United States, 1992-2007. BMC Cancer. 2011;11:325. [DOI:10.1186/1471-2407-11-325] [PMID] [PMCID]
6. Nelson J,BurchfielC, Fekedulegn D,Andrew M. Potential risk factors for incident glioblastoma multiforme: The Honolulu Heart Program and Honolulu-Asia Aging Study. J Neuro-Oncol. 2012; 109: 315-21. [DOI:10.1007/s11060-012-0895-3] [PMID] [PMCID]
7. Mason M,Laperriere N,Wick W, et al., Glioblastoma in the elderly: making sense of the evidence. Neuro-Oncol Pract. 2015; 3(2): 77-86. [DOI:10.1093/nop/npv027] [PMID] [PMCID]
8. Louis D,Perry A,Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathologica. 2016;131(6): 803-20. [DOI:10.1007/s00401-016-1545-1] [PMID]
9. Louis DN. Molecular pathology of malignant gliomas. Annu Rev Pathol. 2006. 1:97-117. [DOI:10.1146/annurev.pathol.1.110304.100043] [PMID]
10. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;359(5): 492-507. [DOI:10.1056/NEJMra0708126] [PMID]
11. Crespo I,Vital A,Tablas M, et al. Molecular and genomic alterations in glioblastoma multiforme. Am J Pathol. 2015;185(7):1820-33. [DOI:10.1016/j.ajpath.2015.02.023] [PMID]
12. Bansal K, Liang M, Rutka J. Molecular biology of human gliomas. Technol Cancer Res Treat. 2006; 5(3): 185-94. [DOI:10.1177/153303460600500302] [PMID]
13. MetibemuD,Akinloye O,Akamo A,Ojo D,Okeowo O,Omotuyi I. Exploring receptor tyrosine kinases-inhibitors in Cancer treatments. EgyptJ Med Human Genet. 2019. 20(1): 35. [DOI:10.1186/s43042-019-0035-0]
14. Zou X,Tang X,Qu Zh, et al. Targeting the PDGF/PDGFR signaling pathway for cancer therapy: A review. Int J Biol Macromol, 2022. 202: 539-57. [DOI:10.1016/j.ijbiomac.2022.01.113] [PMID]
15. Ranza E,Mazzini G,Facoetti A,Nano R. In-vitro effects of the tyrosine kinase inhibitor imatinib on glioblastoma cell proliferation. J Neurooncol, 2010. 96(3): 349-57. [DOI:10.1007/s11060-009-9975-4] [PMID]
16. Zhang P,Xia Q,Liu L,Li Sh,Dong L.Current opinion on molecular characterization for GBM classification in guiding clinical diagnosis, prognosis, and therapy. Front Mol Biosci.2020;7: 562798. [DOI:10.3389/fmolb.2020.562798] [PMID] [PMCID]
17. Koschmann C,Zamler D,Mackay A, et al. Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma. Oncotarget. 2016;7(40): 65696-706. [DOI:10.18632/oncotarget.11602] [PMID] [PMCID]
18. Shih AH , Holland EC. Platelet-derived growth factor (PDGF) and glial tumorigenesis.Cancer Lett. 2006. 232:139-147. [DOI:10.1016/j.canlet.2005.02.002] [PMID]
19. Fomchenko EI,Holland EC. Platelet-derived growth factor-mediated gliomagenesis and brain tumor recruitment. Neurosurg Clin N Am. 2007;18: 39-58. [DOI:10.1016/j.nec.2006.10.006] [PMID]
20. Martinho O, Longatto A,Lambros M, et al. Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomas. Br J Cancer.2009. 101(6): 973-82. [DOI:10.1038/sj.bjc.6605225] [PMID] [PMCID]
21. Jackson EL,Verdugo J,Perotin S, et al. PDGFR alpha- positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron. 2006; 51(2): 187-99. [DOI:10.1016/j.neuron.2006.06.012] [PMID]
22. Lasota J,Mieszkowska A,Sobin L,Miettinen M. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest. 2004. 84(7): 874-83. [DOI:10.1038/labinvest.3700122] [PMID]
23. PietrasK,Sjoblom T,Rubin K,Heldin C,Ostman A. PDGF receptors as cancer drug targets. Cancer Cell. 2003;3(5): 439-43. [DOI:10.1016/S1535-6108(03)00089-8] [PMID]
24. Capdeville R,Buchdunger E,Zimmermann J, et al. Glivec (STI571, Imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 1: 493-502. [DOI:10.1038/nrd839] [PMID]
25. Buchdunger E, O'Reilly T, Wood J. Pharmacology of imatinib (STI571). Eur J Cancer. 2002; 38 Suppl 5: S28-36. [DOI:10.1016/S0959-8049(02)80600-1] [PMID]
26. Reardon DA,Dresemann G,Taillibert S, et al. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. Br J Cancer. 2009;101(12): 1995-2004. [DOI:10.1038/sj.bjc.6605411] [PMID] [PMCID]
27. Raymond E,Brandes A,Dittrich Ch, et al. Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study. J Clin Oncol. 2008;26(28): 4659-65. [DOI:10.1200/JCO.2008.16.9235] [PMID] [PMCID]
28. Wen PY,Yung W,Lamborn K, et al. Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res. 2006;12(16): 4899-4907. [DOI:10.1158/1078-0432.CCR-06-0773] [PMID]
29. Cancer Genome Atlas Research Network.Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature.2008; 455(7216): 1061-68. [DOI:10.1038/nature07385] [PMID] [PMCID]
30. VerhaakR,Hoadley K,Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1): 98-110. [DOI:10.1016/j.ccr.2009.12.020] [PMID] [PMCID]
31. Shen S,Feng Sh,Liu H,Jiang J,Yu X. Associations of histological and molecular alterations with invasion of the corpus callosum in gliomas. Acta Neurochirurgica. 2020;162(7): 1691-99. [DOI:10.1007/s00701-020-04376-9] [PMID]
32. Estevez-Garcia P,Castano A,Martin A, et al. PDGFRα/β and VEGFR2 polymorphisms in colorectal cancer: incidence and implications in clinical outcome. BMC Cancer.2012;12(1): 514. [DOI:10.1186/1471-2407-12-514] [PMID] [PMCID]
33. Trojani A,Ripamonti C,Penco S, et al. Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorphism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation. Anticancer Res.2008;28(5A): 2745-51.
34. LongattoF,Pinheiro C,Martino O, et al. Molecular characterization of EGFR, PDGFRA and VEGFR2 in cervical adenosquamous carcinoma. BMC Cancer. 2009;9(1): 212. [DOI:10.1186/1471-2407-9-212] [PMID] [PMCID]
35. Reis R,Martins A,Ribeiro S, et al. Molecular characterization of PDGFR-α/PDGF-A and c-KIT/SCF in gliosarcomas. Cell Oncol. 2005;27(5-6): 319-26. [DOI:10.1155/2005/347863] [PMID] [PMCID]
36. AppinCL,Gao J,Chisolm C, et al. Glioblastoma with oligodendroglioma component (GBM-O): molecular genetic and clinical characteristics. Brain Pathol.2013;23(4): 454-61. [DOI:10.1111/bpa.12018] [PMID] [PMCID]
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Journal of Advances in Medical and Biomedical Research

Designed & Developed by : Yektaweb