Skip to main content Skip to main navigation menu Skip to site footer

Peranan p53 dalam perkembangan dan prognosis osteosarkoma: tinjauan pustaka



Abstract

Background: Osteosarcoma is the most common non hematopoietic primary malignant tumor in the bone. Several factors have been related through the development and prognosis of osteosarcoma. One of them is the mutation of p53 gene that encodes p53 protein. This literature review aims to evaluate the role p53 in the progressiveness and prognosis of osteosarcoma.

Methods: A review of relevant literature was performed to elaborate p53 involvement in osetosarcoma. A total of 22 qualified published literature from 2006 until 2017 were collected from several electronic database as well as manual search and included in this review.

Results: P53 has an important role in maintaining genome integrity through its ability to induce genes involved in senescence process, DNA repair and apoptosis. Loss of P53 induces progenitor cells to proliferate and experience differentiation disturbances thereby increasing the potential malignant transformation to osteosarcoma. Loss of p53 also increases osteosarcoma progression by increasing proliferation and providing a good microenvironment for tumor cells. P53 causes inhibition to other tumor suppressor proteins such as BMP-2 and CD137L. Loss of P53 has a role in providing a good microenvironment for osteosarcoma cells to invade surrounding tissue, metastasis and suppressed immune response through increased activity of SDF-1, HIF-1α, VEGF, and NO. High mutant p53 expression has a positive association with short-term survival but does not have a strong association to predict long-term survival.

Conclusion: A p53 gene has a pivotal role in the progressiveness and prognosis of osteosarcoma through increasing proliferation and providing a good microenvironment for tumor cells

 

Latar Belakang: Osteosarkoma merupakan tumor ganas primer non hematopoietik tersering pada tulang. Berbagai faktor telah dikaitkan dengan perkembangan dan prognosis pasien osteosarkoma, Salah satunya adalah mutasi gen p53 yang menyandi protein p53. Tinjauan pustaka ini bertujuan untuk mengevaluasi peran p53 dalam progresif dan prognosis osteosarkoma.

Metode: Tinjauan pustaka yang relevan dilakukan untuk menguraikan keterlibatan p53 dalam osetosarcoma. Sebanyak 22 literatur yang diterbitkan berkualitas dari 2006 hingga 2017 dikumpulkan dari beberapa basis data elektronik serta pencarian manual dan dimasukkan dalam ulasan ini.

Hasil: P53 mempunyai peranan yang sangat penting dalam menjaga integritas genom melalui kemampuannya untuk menginduksi gen-gen yang terlibat dalam proses penuaan sel, perbaikan DNA maupun apoptosis. Hilangnya p53 menginduksi sel-sel progenitor osteosarkoma untuk berproliferasi dan mengalami gangguan diferensiasi sehingga meningkatkan potensi transformasi keganasan menjadi osteosarkoma. Kehilangan p53 juga meningkatkan progresivitas osteosarkoma melalui peningkatan proliferasi dan penyediaan lingkungan mikro yang baik bagi sel tumor. P53 menyebabkan hambatan fungsi protein penekan tumor lainnya yaitu BMP-2 dan CD137L. Kehilangan p53 berperan dalam menyediakan lingkungan mikro yang baik untuk sel-sel osteosarkoma untuk menginvasi jaringan sekitar, bermetastasis dan menghambat aktivitas sistem imun melalui peningkatan aktivitas SDF-1, HIF-1α, VEGF, dan NO. Ekspresi p53 mutan yang tinggi memiliki hubungan positif dengan angka harapan hidup jangka pendek namun tidak memiliki hubungan yang kuat untuk memprediksi harapan hidup jangka panjang.

Kesimpulan: Gen p53 memiliki peran penting dalam progresivitas dan prognosis osteosarkoma melalui peningkatan proliferasi dan menyediakan lingkungan mikro yang baik untuk sel tumor.

Keywords: p53 osteosarkoma progresivitas prognosis

References

  1. Picci P. Osteosarcoma (Osteogenic sarcoma). Orphanet J Rare Dis. 2007;2:6.
  2. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. WHO Classification of Tumours of Soft Tissue and Bone. Lyon: IARC; 2013.
  3. Folpe AL, Inwards CY. Bone and Soft Tissue Pathology. Philadelphia: Elsevier Saunders; 2010.
  4. Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia: Saunders Elsevier; 2015.
  5. Velletri T, Xie N, Wang Y, Huang Y, Yang Q, Chen X, et al. P53 functional abnormality in mesenchymal stem cells promotes osteosarcoma development. Cell Death Dis. 2016;7:e2015.
  6. Rao-bindal K, Kleinerman ES. Epigenetic Regulation of apoptosis and cell cycle in osteosarcoma. Sarcoma. 2011;2011:679457.
  7. Wang L, Liu Z, Jing P, Shao L, Chen L, He X, et al. Effects of murine double minute 2 polymorphisms on the risk and survival of osteosarcoma : a systemic review and meta-analysis. Tumour Biol. 2014;35(2):1649-52.
  8. Walkley CR, Qudsi R, Sankaran VG, Perry JA, Gostissa M, Roth SI, et al. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb , mimics the human disease. Genes Dev. 2008:22(12);1662–76.
  9. Rubio R, Gutierrez-Aranda I, Sáez-Castillo AI, Labarga A, Rosu-Myles M, Gonzalez-Garcia S, et al. The differentiation stage of p53-Rb-deficient bone marrow mesenchymal stem cells imposes the phenotype of in vivo sarcoma development. Oncogene. 2012;32(41):4970–80.
  10. Dudley AC, Shih SC, Cliffe AR, Hida K, Klagsbrun M. Attenuated p53 activation in tumour-associated stromal cells accompanies decreased sensitivity to etoposide and vincristine. Br J Cancer. 2008;99(1):118–125.
  11. Tsuda Y, Tanikawa C, Miyamoto T, Hirata M, Yodsurang V, Zhang YZ, et al. Identification of a p53 target, CD137L, that mediates growth suppression and immune response of osteosarcoma cells. Sci Rep. 2017;7(1):10739.
  12. Huang Y, Yu P, Li W, Ren G, Roberts AI, Cao W, et al. p53 regulates mesenchymal stem cell-mediated tumor suppression in a tumor microenvironment through immune modulation. Oncogene. 2014;33(29):3830–3838.
  13. Moskovits N, Kalinkovich A, Bar J, Lapidot T, Oren M. p53 Attenuates Cancer cell migration and invasion through repression of SDF-1 / CXCL12 Expression in stromal fibroblasts. Cancer Res. 2006;66(22):10671–6
  14. Ren H, Zhang Y, Li H, Xie T, Sun L, Zhu T, et al. Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma : a meta-analysis. Onco Targets Ther. 2016;9:1477–1487.
  15. Coimbra IB, Jimenez SA, Hawkins DF, Piera-Velazquez S, Stokes DG. Hypoxia inducible factor-1 alpha expression in human normal and osteoarthritic chondrocytes. Osteoarthritis Cartilage. 2004;12(4):336-45.
  16. Toffoli G, Biason P, Russo A, De Mattia E, Cecchin E, Hattinger CM, et al. Effect of TP53 Arg72Pro and MDM2 SNP309 polymorphisms on the risk of high-grade osteosarcoma development and survival. Clin Cancer Res. 2009;15(10):3550–6.
  17. Boulytcheva IV, Soloviev YN, Kushlinskii NE, Mahson AN. Expression of Molecular Markers in the Tumor and Survival Prognosis in Osteosarcoma. Bull Exp Biol Med. 2010;150(2):237–42.
  18. Wu X, Cai ZD, Lou LM, Zhu YB. Expressions of p53, c-MYC, BCL-2 and apoptotic index in human osteosarcoma and their correlations with prognosis of patients. Cancer Epidemiol. 2012;36(2):212–6.
  19. Wu X, Cheng B, Cai ZD, Lou LM. Determination of the apoptotic index in osteosarcoma tissue and its relationship with patients prognosis. Cancer Cell Int. 2013;13(1):56.
  20. Fu HL, Shao L, Wang Q, Jia T, Li M, Yang DP. A systematic review of p53 as a biomarker of survival in patients with osteosarcoma. Tumor Biol. 2013;34(6):3817–21.
  21. Jiang L, Tao C, He A. Prognostic significance of p53 expression in malignant bone tumors: a meta-analysis. Tumor Biology. 2013;34(2):1037–43.
  22. Yao D, Cai G, Chen J, Ling R, Wu S, Li Y. Prognostic value of p53 alterations in human osteosarcoma: a meta analysis. 2014;7(10):6725–33.

How to Cite

Sumadi, I. W. J., & Adiputra, N. (2020). Peranan p53 dalam perkembangan dan prognosis osteosarkoma: tinjauan pustaka. Intisari Sains Medis, 11(1), 41–46. https://doi.org/10.15562/ism.v11i1.536
ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver
Download Citation
Endnote/Zotero/Mendeley (RIS) BibTeX

HTML
384

Total
2734

Share

Search Panel

I Wayan Juli Sumadi
Google Scholar
Pubmed
ISM Journal

Nyoman Adiputra
Google Scholar
Pubmed
ISM Journal