The Difference of Hypoxia Inducible Factor 2α mRNA Expression in High-Grade and Low-Grade Glioma Tissue

Bagus Ramasha Amangku -  Undergraduate Student of International Class Program Faculty of Medicine, Universitas Indonesia, Jakart, Indonesia
Syaiful Ichwan -  Department of Neurosurgery Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
Septelia Inawati Wanandi -  Department of Biochemistry and Molecular Biology Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
Novi Silvia Hardiany* -  Department of Biochemistry and Molecular Biology Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia

DOI : 10.33371/ijoc.v13i2.633

Background: HIF-2α is a transcription factor in hypoxic condition, and high expression levels of it correlate with the concepts of metastasis, therapy opposition and reduced quality of prognosis in various forms of cancerous growth. Due to the exceedingly infiltrative ability of brain glioma cells, gliomas cannot be completely deteriorated with surgery and the relapse rate is high. This study goal to identify the relative expression of HIF-2α gene in the direction of glioma malignancy and its classification.

Methods: Specimens used in this research comprise of 20 glioma samples obtained from glioma patients in Cipto Mangunkusumo Hospital. Relative expression of HIF-2α was measured by utilizing quantitative Real Time-Polymerase Chain Reaction (RT-PCR). Cycle threshold (CT) values were achieved correlated with the amplified DNA, and then the relative expression was attained by using Livak method of calculation.

Results: The results produced a greater average of relative expression of HIF-2α in the grade III and IV types (18.64; n=7) rather than in the lower grades (5.68; n=13). However, the data is statistically inconsequential.

Conclusions: High-grade glioma tends to express HIF-2α mRNA higher compared to the lower grade. Therefore, it is possible to use HIF-2α as a prognostic marker for glioma- diagnosed patients, although additional experiments need to be performed to strengthen these facts.

HIF-2α, mRNA expression, glioma
  1. McFaline-Figueroa JR, Lee EQ. Brain tumors. Am J Med. 2018;131(8):874-82.
  2. Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, et al. The epidemiology of glioma in adults: a “state of the science” review. Neuro Oncol. 2014;16(7):896-913.
  3. Llaguno SR, Parada LF. Cell of origin of glioma: biological and clinical implications. Br J Cancer. 2016;115(12):1445.
  4. Louis DN, Perry A, Reifenberger G, Von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta neuropathol. 2016;131(6):803-20.
  5. Munthe S, Petterson SA, Dahlrot RH, Poulsen FR, Hansen S, Kristensen BW. Glioma cells in the tumor periphery have a stem cell phenotype. PloS one. 2016;11(5):e0155106.
  6. Aman RA. Identification on predictive factors of the radiosensitivity of glial cell tumour: A review on angiogenesis, cell proliferation and apoptosis as behaviours of biologic tumour. [Dissertation]. Jakarta: Faculty of Medicine Universitas Indonesia; 2008.
  7. Li Z, Rich JN. Hypoxia and hypoxia inducible factors in cancer stem cell maintenance. In: Diverse effects of hypoxia on tumor progression. Springer Berlin Heidelberg. 2010:p. 21-30.
  8. Rockwell S, Dobrucki IT, Kim EY, Marrison ST, Vu VT. Hypoxia and radiation therapy: past history, ongoing research, and future promise. Curr Mol Med. 2009;9(4):442-58.
  9. McNamee EN, Johnson DK, Homann D, Clambey ET. Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function. Immunol Res. 2013;55(1-3):58-70.
  10. Hamid F, Hardiany N, Hikmah F, Ichwan S. Relative expression of C-MYC mRNA in human glioma cells related to the degree of malignancy. eJournal Kedokt Indones. 2017;5(2):85-90.
  11. Paramita R. Peran hypoxia inducible factor (HIF) terhadap ketahanan hidup sel kanker payudara manusia T47D melalui pengaturan sitokrom-c dan surviving. 2014; (in Dissertation).
  12. Hardiany NS, Sadikin M, Siregar N, Wanandi SI. The suppression of manganese superoxide dismutase decreased the survival of human glioblastomamultiforme T98G cells. Med J of Indonesia. 2017;26(1):19-26.
  13. Livak K, Schmittgen T. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25:402-8.
  14. Chen J, Zhou C, Lin Z. The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients. J Neurol Sci. 2015;356:148-52.
  15. Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. Differential roles of hypoxia-inducible factor 1α (HIF-1α) and HIF-2α in hypoxic gene regulation. Mol Cell Biol. 2003;23(24):9361-74.
  16. Han S, Huang T, Li W, Liu S, Yang W, Shi Q, et al. Association between hypoxia-inducible factor-2α (HIF-2α) expression and colorectal cancer and its prognostic role: a systematic analysis. Cell Physiol Biochem. 2018;48:516-27.
  17. Schodel J, Grampp S, Maher ER, Moch H, Ratcliffe PJ, Russo P, et al. Hypoxia, hypoxia-inducible transcription factors, and renal cancer. Eur Urol. 2016;69(4):646-57.
  18. Hu G, Wei B, Wang L, Wang L, Kong D, Jin Y, et al. Analysis of gene expression profiles associated with glioma progression. Mol Med Rep. 2015;12(2):1884-90.
  19. El Guerrab A, Cayre A, Kwiatkowski F, Privat M, Rossignol JM, Rossignol F, et al. Quantification of hypoxia-related gene expression as a potential approach for clinical outcome prediction in breast cancer. PloS one. 2017;12(4):e0175960.
  20. Covello KL, Kehler J, Yu H, Gordan JD, Arsham AM, Hu CJ, et al. HIF-2α regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 2006;20(5):557-70.

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Submitted: 2019-03-29
Published: 2019-07-13
Section: Research Articles
Article Statistics: 124 112