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Published in: International Journal of Clinical Oncology 11/2019

01-11-2019 | osteosarcoma | Original Article

CDC20 and its downstream genes: potential prognosis factors of osteosarcoma

Authors: Man-si Wu, Qing-yu Ma, Dong-dong Liu, Xiao-juan Li, Li-juan Deng, Nan Li, Jingnan Shen, Zhiqiang Zhao, Jia-xu Chen

Published in: International Journal of Clinical Oncology | Issue 11/2019

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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.
Appendix
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Literature
1.
go back to reference Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Treatment (PDQ(R)) (2002) Health Professional Version, in PDQ Cancer Information Summaries. Bethesda (MD). Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Treatment (PDQ(R)) (2002) Health Professional Version, in PDQ Cancer Information Summaries. Bethesda (MD).
2.
go back to reference 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):1531–1543CrossRef 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):1531–1543CrossRef
3.
go back to reference Isakoff MS et al (2015) Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol 33(27):3029–3035CrossRef Isakoff MS et al (2015) Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol 33(27):3029–3035CrossRef
4.
go back to reference Kuijjer ML et al (2013) IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma. BMC Cancer 13:245CrossRef Kuijjer ML et al (2013) IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma. BMC Cancer 13:245CrossRef
5.
go back to reference McLean JR et al (2011) State of the APC/C: organization, function, and structure. Crit Rev Biochem Mol Biol 46(2):118–136CrossRef McLean JR et al (2011) State of the APC/C: organization, function, and structure. Crit Rev Biochem Mol Biol 46(2):118–136CrossRef
6.
go back to reference Stemmann O et al (2001) Dual inhibition of sister chromatid separation at metaphase. Cell 107(6):715–726CrossRef Stemmann O et al (2001) Dual inhibition of sister chromatid separation at metaphase. Cell 107(6):715–726CrossRef
7.
go back to reference Bharadwaj R, Yu H (2004) The spindle checkpoint, aneuploidy, and cancer. Oncogene 23(11):2016–2027CrossRef Bharadwaj R, Yu H (2004) The spindle checkpoint, aneuploidy, and cancer. Oncogene 23(11):2016–2027CrossRef
8.
go back to reference 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):792–801CrossRef 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):792–801CrossRef
9.
go back to reference Shirayama M et al (1999) APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5. Nature 402(6758):203–207CrossRef Shirayama M et al (1999) APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5. Nature 402(6758):203–207CrossRef
10.
go back to reference 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):137–148CrossRef 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):137–148CrossRef
11.
go back to reference Nasmyth K (2002) Segregating sister genomes: the molecular biology of chromosome separation. Science 297(5581):559–565CrossRef Nasmyth K (2002) Segregating sister genomes: the molecular biology of chromosome separation. Science 297(5581):559–565CrossRef
12.
go back to reference Nam HJ, van Deursen JM (2014) Cyclin B2 and p53 control proper timing of centrosome separation. Nat Cell Biol 16(6):538–549CrossRef Nam HJ, van Deursen JM (2014) Cyclin B2 and p53 control proper timing of centrosome separation. Nat Cell Biol 16(6):538–549CrossRef
13.
go back to reference Shannon P et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504CrossRef Shannon P et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504CrossRef
14.
go back to reference Pakos EE et al (2009) Prognostic factors and outcomes for osteosarcoma: an international collaboration. Eur J Cancer 45(13):2367–2375CrossRef Pakos EE et al (2009) Prognostic factors and outcomes for osteosarcoma: an international collaboration. Eur J Cancer 45(13):2367–2375CrossRef
15.
go back to reference 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):2303–2312CrossRef 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):2303–2312CrossRef
16.
go back to reference Gorlick R et al (1999) Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol 17(9):2781–2788CrossRef Gorlick R et al (1999) Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol 17(9):2781–2788CrossRef
17.
go back to reference Onda M et al (1996) ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer 77(1):71–78CrossRef Onda M et al (1996) ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer 77(1):71–78CrossRef
18.
go back to reference Kilpatrick SE et al (2001) Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma. Mod Pathol 14(12):1277–1283CrossRef Kilpatrick SE et al (2001) Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma. Mod Pathol 14(12):1277–1283CrossRef
19.
go back to reference 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):467–472CrossRef 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):467–472CrossRef
20.
go back to reference 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):1205–1214PubMed 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):1205–1214PubMed
21.
go back to reference Goto A et al (1998) Association of loss of heterozygosity at the p53 locus with chemoresistance in osteosarcomas. Jpn J Cancer Res 89(5):539–547CrossRef Goto A et al (1998) Association of loss of heterozygosity at the p53 locus with chemoresistance in osteosarcomas. Jpn J Cancer Res 89(5):539–547CrossRef
22.
go back to reference 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):1459–1468PubMed 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):1459–1468PubMed
23.
go back to reference 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):43–52CrossRef 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):43–52CrossRef
24.
go back to reference Gao Y et al (2018) Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells. Oncol Rep 40(2):841–848PubMed Gao Y et al (2018) Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells. Oncol Rep 40(2):841–848PubMed
25.
go back to reference Hu K et al (2014) Targeting the anaphase-promoting complex/cyclosome (APC/C)- bromodomain containing 7 (BRD7) pathway for human osteosarcoma. Oncotarget 5(10):3088–3100CrossRef Hu K et al (2014) Targeting the anaphase-promoting complex/cyclosome (APC/C)- bromodomain containing 7 (BRD7) pathway for human osteosarcoma. Oncotarget 5(10):3088–3100CrossRef
26.
go back to reference Yu H (2007) Cdc20: a WD40 activator for a cell cycle degradation machine. Mol Cell 27(1):3–16CrossRef Yu H (2007) Cdc20: a WD40 activator for a cell cycle degradation machine. Mol Cell 27(1):3–16CrossRef
27.
go back to reference 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):599–607CrossRef 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):599–607CrossRef
28.
go back to reference Penas C, Ramachandran V, Ayad NG (2011) The APC/C ubiquitin ligase: from cell biology to tumorigenesis. Front Oncol 1:60PubMed Penas C, Ramachandran V, Ayad NG (2011) The APC/C ubiquitin ligase: from cell biology to tumorigenesis. Front Oncol 1:60PubMed
29.
go back to reference Karra H et al (2014) Cdc20 and securin overexpression predict short-term breast cancer survival. Br J Cancer 110(12):2905–2913CrossRef Karra H et al (2014) Cdc20 and securin overexpression predict short-term breast cancer survival. Br J Cancer 110(12):2905–2913CrossRef
30.
go back to reference Shekhar R et al (2019) The microRNAs miR-449a and miR-424 suppress osteosarcoma by targeting cyclin A2 expression. J Biol Chem 294(12):4381–4400CrossRef Shekhar R et al (2019) The microRNAs miR-449a and miR-424 suppress osteosarcoma by targeting cyclin A2 expression. J Biol Chem 294(12):4381–4400CrossRef
31.
go back to reference 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):5235–5249CrossRef 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):5235–5249CrossRef
32.
go back to reference Navid F et al (2017) A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy. Int J Cancer 141(7):1469–1477CrossRef Navid F et al (2017) A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy. Int J Cancer 141(7):1469–1477CrossRef
33.
go back to reference 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):1298–1308CrossRef 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):1298–1308CrossRef
34.
go back to reference 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):2800–2808CrossRef 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):2800–2808CrossRef
35.
go back to reference 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):e90795CrossRef 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):e90795CrossRef
Metadata
Title
CDC20 and its downstream genes: potential prognosis factors of osteosarcoma
Authors
Man-si Wu
Qing-yu Ma
Dong-dong Liu
Xiao-juan Li
Li-juan Deng
Nan Li
Jingnan Shen
Zhiqiang Zhao
Jia-xu Chen
Publication date
01-11-2019
Publisher
Springer Singapore
Published in
International Journal of Clinical Oncology / Issue 11/2019
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-019-01500-3

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