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Published in: Journal of Neuro-Oncology 1/2017

01-05-2017 | Laboratory Investigation

CDC20 with malignant progression and poor prognosis of astrocytoma revealed by analysis on gene expression

Authors: Yiming Ding, Shuqing Yu, Zhaoshi Bao, Yanwei Liu, Tingyu Liang

Published in: Journal of Neuro-Oncology | Issue 1/2017

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Abstract

The malignant transformation of astrocytoma may result from the accumulation of multiple genetic alterations. Current research shows that diffuse astrocytoma (AIIs, WHO grade II) is inherently predisposed to recur locally, and to spontaneously progress to anaplastic astrocytoma (AAIIIs, WHO grade III) and eventually secondary glioblastoma (sGBMIVs, WHO grade IV). The aim of the study was to identify and validate the important gene(s) associated with malignant progression and poor prognosis of astrocytoma. Average expression levels of 82 samples (35 AIIs, 13 AAIIIs and 34 sGBMIVs) were compared to each other through no-paired student test. Candidate genes were screened by DAVID and Kaplan–Meier survival analysis. Further, the significant candidate genes were validated through real-time PCR(qPCR), western blot and immunohistochemistry (IHC) in different grades of glioma. Finally, the association of target gene and clinical molecular characterization was analyzed by Chi-squared analysis. The cell-division cycle protein 20(CDC20, p = 0.0129) and the polo-like kinase 1(PLK1, p = 0.0046) were screened by statistical and Kaplan–Meier survival analysis. The expression levels of CDC20 and PLK1 rose significantly through real-time PCR(qPCR), western blot and IHC. A chi-squared analysis showed that patients with CDC20 high-expression differ from patients with CDC20 low-expression in terms of WHO classification (p < 0.0001), karnofsky performance score (KPS, p < 0.0001), isocitrate dehydrogenase mutation (IDH1, p < 0.0001), phosphatase and tensin homolog mutation (PTEN, p = 0.027) and epidermal growth factor receptor protein amplification (EGFR, p = 0.048). Moreover, the biological processes analyses indicate CDC20 might have an essential role in astrocyte cell proliferation. We demonstrated that the expression level of CDC20 increases significantly along with malignant progression and poor prognosis of astrocytoma.
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Literature
1.
2.
go back to reference Floris H. Hendrikus J. Cathleen R et al (2011) MGMT promoter hypermethylation is a frequent, early, and consistent event in astrocytoma progression, and not correlated with TP53 mutation. J Neurooncol 101:405–417CrossRef Floris H. Hendrikus J. Cathleen R et al (2011) MGMT promoter hypermethylation is a frequent, early, and consistent event in astrocytoma progression, and not correlated with TP53 mutation. J Neurooncol 101:405–417CrossRef
3.
go back to reference Haque A, Banik NL, Ray SK et al (2011) Molecular alterations in glioblastoma: potential targets for immunotherapy. Prog Mol Biol Transl Sci 98:187–234CrossRefPubMedPubMedCentral Haque A, Banik NL, Ray SK et al (2011) Molecular alterations in glioblastoma: potential targets for immunotherapy. Prog Mol Biol Transl Sci 98:187–234CrossRefPubMedPubMedCentral
4.
go back to reference Liu Y, Hu H, Jiang T et al (2014) Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas. Oncotarget 5(24):12593–12606CrossRefPubMedPubMedCentral Liu Y, Hu H, Jiang T et al (2014) Multidimensional analysis of gene expression reveals TGFB1I1-induced EMT contributes to malignant progression of astrocytomas. Oncotarget 5(24):12593–12606CrossRefPubMedPubMedCentral
5.
go back to reference Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57CrossRef Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57CrossRef
6.
go back to reference Chang DZ, Ma Y, Ji B, Liu Y et al (2012) Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. J Hematol Oncol 5:15CrossRefPubMedPubMedCentral Chang DZ, Ma Y, Ji B, Liu Y et al (2012) Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. J Hematol Oncol 5:15CrossRefPubMedPubMedCentral
7.
9.
10.
go back to reference Ding Z-Y, Wu H-R, Zhang J-M et al (2014) Expression characteristics of CDC20 in gastric cancer and its correlation with poor prognosis. Int J Clin Exp Pathol 7(2):722–727PubMedPubMedCentral Ding Z-Y, Wu H-R, Zhang J-M et al (2014) Expression characteristics of CDC20 in gastric cancer and its correlation with poor prognosis. Int J Clin Exp Pathol 7(2):722–727PubMedPubMedCentral
11.
go back to reference Chang DZ, Ma Y, Ji B, Liu Y, Hwu P, Abbruzzese JL, Logsdon C, Wang H (2012) Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. J Hematol Oncol 5:15CrossRefPubMedPubMedCentral Chang DZ, Ma Y, Ji B, Liu Y, Hwu P, Abbruzzese JL, Logsdon C, Wang H (2012) Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. J Hematol Oncol 5:15CrossRefPubMedPubMedCentral
12.
go back to reference Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M (2012) Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients. J Surg Oncol 106(4):423–430CrossRefPubMed Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M (2012) Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients. J Surg Oncol 106(4):423–430CrossRefPubMed
13.
go back to reference Bie L, Zhao G, Cheng P, Rondeau G, Porwollik S, Ju Y, Xia XQ, McClelland M (2011) The accuracy of survival time prediction for patients with glioma is improved by measuring mitotic spindle checkpoint gene expression. PLoS ONE 6(10):e25631CrossRefPubMedPubMedCentral Bie L, Zhao G, Cheng P, Rondeau G, Porwollik S, Ju Y, Xia XQ, McClelland M (2011) The accuracy of survival time prediction for patients with glioma is improved by measuring mitotic spindle checkpoint gene expression. PLoS ONE 6(10):e25631CrossRefPubMedPubMedCentral
14.
go back to reference Mondal G, Sengupta S, Panda CK, Gollin SM, Saunders WS, Roychoudhury S (2007) Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Carcinogenesis 28(1):81–92CrossRefPubMed Mondal G, Sengupta S, Panda CK, Gollin SM, Saunders WS, Roychoudhury S (2007) Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Carcinogenesis 28(1):81–92CrossRefPubMed
17.
go back to reference Marucci G, Morandi L, Magrini E et al (2008) Gene expression profiling in glioblastoma and immunohistochemical evaluation of IGFBP-2 and CDC20. Virchows Arch 453:599–609CrossRefPubMed Marucci G, Morandi L, Magrini E et al (2008) Gene expression profiling in glioblastoma and immunohistochemical evaluation of IGFBP-2 and CDC20. Virchows Arch 453:599–609CrossRefPubMed
18.
go back to reference Sunkel CE, Glover DM (1988) Polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J Cell Sci 89(Pt 1):25–38PubMed Sunkel CE, Glover DM (1988) Polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J Cell Sci 89(Pt 1):25–38PubMed
20.
go back to reference Strebhardt K (2010) Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov 9(8):643–660CrossRefPubMed Strebhardt K (2010) Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov 9(8):643–660CrossRefPubMed
21.
go back to reference Tandle AT et al (2013) Inhibition of PLK1 in glioblastoma multiforme induces mitotic catastrophe and enhances radiosensitization. Eur J Cancer 49(14):3020–3028CrossRefPubMedPubMedCentral Tandle AT et al (2013) Inhibition of PLK1 in glioblastoma multiforme induces mitotic catastrophe and enhances radiosensitization. Eur J Cancer 49(14):3020–3028CrossRefPubMedPubMedCentral
Metadata
Title
CDC20 with malignant progression and poor prognosis of astrocytoma revealed by analysis on gene expression
Authors
Yiming Ding
Shuqing Yu
Zhaoshi Bao
Yanwei Liu
Tingyu Liang
Publication date
01-05-2017
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2017
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-017-2434-8

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