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International Journal of Clinical Oncology

, Volume 24, Issue 11, pp 1479–1489 | Cite as

CDC20 and its downstream genes: potential prognosis factors of osteosarcoma

  • Man-si Wu
  • Qing-yu Ma
  • Dong-dong Liu
  • Xiao-juan Li
  • Li-juan Deng
  • Nan Li
  • Jingnan Shen
  • Zhiqiang ZhaoEmail author
  • Jia-xu ChenEmail author
Original Article

Abstract

Background

We investigated the microarray data GSE42352 to identify genes that can be used as prognosis factors in osteosarcoma.

Methods

Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of Cytoscape ClueGo were used in verifying the function of different genes. Realtime-PCR were used to confirm the microarray results. 83 patient samples were collected and underwent Kaplan–Meier survival analysis and multivariate analysis to predict the prospect of genes using as prognosis factors.

Results

After analyzing the microarray data GSE42352, mitosis metaphase to anaphase-related genes CDC20, securin, cyclin A2 and cyclin B2 were found to be overexpressed in osteosarcoma cell lines. Kaplan–Meier survival analysis showed that overexpression of these genes can predict poor prognosis outcomes in osteosarcoma patients. Furthermore, any combination of the four genes seems to be more effective in predicting osteosarcoma outcomes than any of these genes alone.

Conclusions

CDC20 and its downstream substracts securin, cyclin A2 and cyclin B2 are good factors that can predict prognosis outcomes in osteosarcoma. Any two combination of these four genes are more effective to be used as osteosarcoma prognosis factors.

Keywords

Osteosarcoma Cell cycle CDC20 Prognosis 

Notes

Acknowledgements

This work was supported by Grants from National Natural Science Foundation of China (nos. 81702943, 81602356), Medical Science and Technology Research Foundation of Guangdong, China (no. A2018543).

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest.

Supplementary material

10147_2019_1500_MOESM1_ESM.docx (19 kb)
Supplementary file1 (DOCX 19 kb)

References

  1. 1.
    Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Treatment (PDQ(R)) (2002) Health Professional Version, in PDQ Cancer Information Summaries. Bethesda (MD).Google Scholar
  2. 2.
    Mirabello L, Troisi RJ, Savage SA (2009) Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer 115(7):1531–1543CrossRefGoogle Scholar
  3. 3.
    Isakoff MS et al (2015) Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol 33(27):3029–3035CrossRefGoogle Scholar
  4. 4.
    Kuijjer ML et al (2013) IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma. BMC Cancer 13:245CrossRefGoogle Scholar
  5. 5.
    McLean JR et al (2011) State of the APC/C: organization, function, and structure. Crit Rev Biochem Mol Biol 46(2):118–136CrossRefGoogle Scholar
  6. 6.
    Stemmann O et al (2001) Dual inhibition of sister chromatid separation at metaphase. Cell 107(6):715–726CrossRefGoogle Scholar
  7. 7.
    Bharadwaj R, Yu H (2004) The spindle checkpoint, aneuploidy, and cancer. Oncogene 23(11):2016–2027CrossRefGoogle Scholar
  8. 8.
    Zur A, Brandeis M (2001) Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis. EMBO J 20(4):792–801CrossRefGoogle Scholar
  9. 9.
    Shirayama M et al (1999) APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5. Nature 402(6758):203–207CrossRefGoogle Scholar
  10. 10.
    Geley S et al (2001) Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. J Cell Biol 153(1):137–148CrossRefGoogle Scholar
  11. 11.
    Nasmyth K (2002) Segregating sister genomes: the molecular biology of chromosome separation. Science 297(5581):559–565CrossRefGoogle Scholar
  12. 12.
    Nam HJ, van Deursen JM (2014) Cyclin B2 and p53 control proper timing of centrosome separation. Nat Cell Biol 16(6):538–549CrossRefGoogle Scholar
  13. 13.
    Shannon P et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504CrossRefGoogle Scholar
  14. 14.
    Pakos EE et al (2009) Prognostic factors and outcomes for osteosarcoma: an international collaboration. Eur J Cancer 45(13):2367–2375CrossRefGoogle Scholar
  15. 15.
    Collins M et al (2013) Benefits and adverse events in younger versus older patients receiving neoadjuvant chemotherapy for osteosarcoma: findings from a meta-analysis. J Clin Oncol 31(18):2303–2312CrossRefGoogle Scholar
  16. 16.
    Gorlick R et al (1999) Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol 17(9):2781–2788CrossRefGoogle Scholar
  17. 17.
    Onda M et al (1996) ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer 77(1):71–78CrossRefGoogle Scholar
  18. 18.
    Kilpatrick SE et al (2001) Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma. Mod Pathol 14(12):1277–1283CrossRefGoogle Scholar
  19. 19.
    Feugeas O et al (1996) Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma. J Clin Oncol 14(2):467–472CrossRefGoogle Scholar
  20. 20.
    Heinsohn S et al (2007) Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma. Int J Oncol 30(5):1205–1214PubMedGoogle Scholar
  21. 21.
    Goto A et al (1998) Association of loss of heterozygosity at the p53 locus with chemoresistance in osteosarcomas. Jpn J Cancer Res 89(5):539–547CrossRefGoogle Scholar
  22. 22.
    Serra M et al (2006) May P-glycoprotein status be used to stratify high-grade osteosarcoma patients? Results from the Italian/Scandinavian Sarcoma Group 1 treatment protocol. Int J Oncol 29(6):1459–1468PubMedGoogle Scholar
  23. 23.
    Shang G, Ma X, Lv G (2018) Cell division cycle 20 promotes cell proliferation and invasion and inhibits apoptosis in osteosarcoma cells. Cell Cycle 17(1):43–52CrossRefGoogle Scholar
  24. 24.
    Gao Y et al (2018) Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells. Oncol Rep 40(2):841–848PubMedGoogle Scholar
  25. 25.
    Hu K et al (2014) Targeting the anaphase-promoting complex/cyclosome (APC/C)- bromodomain containing 7 (BRD7) pathway for human osteosarcoma. Oncotarget 5(10):3088–3100CrossRefGoogle Scholar
  26. 26.
    Yu H (2007) Cdc20: a WD40 activator for a cell cycle degradation machine. Mol Cell 27(1):3–16CrossRefGoogle Scholar
  27. 27.
    Ouellet V et al (2006) Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer. Int J Cancer 119(3):599–607CrossRefGoogle Scholar
  28. 28.
    Penas C, Ramachandran V, Ayad NG (2011) The APC/C ubiquitin ligase: from cell biology to tumorigenesis. Front Oncol 1:60PubMedGoogle Scholar
  29. 29.
    Karra H et al (2014) Cdc20 and securin overexpression predict short-term breast cancer survival. Br J Cancer 110(12):2905–2913CrossRefGoogle Scholar
  30. 30.
    Shekhar R et al (2019) The microRNAs miR-449a and miR-424 suppress osteosarcoma by targeting cyclin A2 expression. J Biol Chem 294(12):4381–4400CrossRefGoogle Scholar
  31. 31.
    Tschop K, Engeland K (2007) Cell cycle-dependent transcription of cyclin B2 is influenced by DNA methylation but is independent of methylation in the CDE and CHR elements. FEBS J 274(20):5235–5249CrossRefGoogle Scholar
  32. 32.
    Navid F et al (2017) A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy. Int J Cancer 141(7):1469–1477CrossRefGoogle Scholar
  33. 33.
    Deng Z et al (2016) Histone deacetylase inhibitor trichostatin a promotes the apoptosis of osteosarcoma cells through p53 signaling pathway activation. Int J Biol Sci 12(11):1298–1308CrossRefGoogle Scholar
  34. 34.
    Shor AC et al (2007) Dasatinib inhibits migration and invasion in diverse human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on SRC kinase for survival. Cancer Res 67(6):2800–2808CrossRefGoogle Scholar
  35. 35.
    Gobin B et al (2014) Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models. PLoS One 9(3):e90795CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Man-si Wu
    • 1
  • Qing-yu Ma
    • 1
  • Dong-dong Liu
    • 1
  • Xiao-juan Li
    • 1
  • Li-juan Deng
    • 1
  • Nan Li
    • 1
  • Jingnan Shen
    • 2
  • Zhiqiang Zhao
    • 2
    Email author
  • Jia-xu Chen
    • 1
    Email author
  1. 1.Formula-Pattern Research Center, School of Traditional Chinese MedicineJinan UniversityGuangzhouChina
  2. 2.Department of Musculoskeletal OncologyThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina

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