CDC20 overexpression leads to poor prognosis in solid tumors

Wang, Shengjie; Chen, Borong; Zhu, Zhipeng; Zhang, Liang; Zeng, Junjie; Liu, Gang; Xiong, Disheng; Luo, Qi; Huang, Zhengjie

doi:10.1097/md.0000000000013832

Cited by 15 publications

(13 citation statements)

References 21 publications

(22 reference statements)

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“…CDC20 is a cell cycle regulating protein. A large number of studies have confirmed that CDC20 is upregulated in solid tumors and promotes cell growth and invasion leading to poor prognosis (Ding et al, 2017; Wang S. et al, 2018). Meanwhile, higher expression of CDC20 was found to be related to a high tumor grade and stage in common malignant tumors including EC (Gayyed et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Crucial Genes Associated With the Pathogenesis and Prognosis of Endometrial Cancer

Liu

Lin

2019

Front. Genet.

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Background and Objective: Endometrial cancer (EC) is a common gynecological malignancy worldwide. Despite advances in the development of strategies for treating EC, prognosis of the disease remains unsatisfactory, especially for advanced EC. The aim of this study was to identify novel genes that can be used as potential biomarkers for identifying the prognosis of EC and to construct a novel risk stratification using these genes. Methods and Results: An mRNA sequencing dataset, corresponding survival data and expression profiling of an array of EC patients were obtained from The Cancer Genome Atlas and Gene Expression Omnibus, respectively. Common differentially expressed genes (DEGs) were identified based on sequencing and expression as given in the profiling dataset. Pathway enrichment analysis of the DEGs was performed using the Database for Annotation, Visualization, and Integrated Discovery. The protein-protein interaction network was established using the string online database in order to identify hub genes. Univariate and multivariable Cox regression analyses were used to screen prognostic DEGs and to construct a prognostic signature. Survival analysis based on the prognostic signature was performed on TCGA EC dataset. A total of 255 common DEGs were found and 11 hub genes (TOP2A, CDK1, CCNB1, CCNB2, AURKA, PCNA, CCNA2, BIRC5, NDC80, CDC20, and BUB1BA) that may be closely related to the pathogenesis of EC were identified. A panel of 7 DEG signatures consisting of PHLDA2, GGH, ESPL1, FAM184A, KIAA1644, ESPL1, and TRPM4 were constructed. The signature performed well for prognosis prediction (p < 0.001) and time-dependent receiver-operating characteristic (ROC) analysis displayed an area under the curve (AUC) of 0.797, 0.734, 0.729, and 0.647 for 1, 3, 5, and 10-year overall survival (OS) prediction, respectively. Conclusion: This study identified potential genes that may be involved in the pathophysiology of EC and constructed a novel gene expression signature for EC risk stratification and prognosis prediction.

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Crucial Genes Associated With the Pathogenesis and Prognosis of Endometrial Cancer

Liu

Lin

2019

Front. Genet.

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“…Thus, targeting CDC20 in cancer may be a potential treatment strategy [31]. Wang et al reported that CDC20 serves as a meaningful prognostic biomarker in most cases of human solid tumours and that its high expression reduces patient survival [32]. HMGA-induced CCNB2 (a molecule of the cyclin clan) plays an important role in the development of mouse or human pituitary tumours [33].…”

Section: Discussionmentioning

confidence: 99%

CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis

Zhang

Jiang

et al. 2019

BMC Med Genomics

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BackgroundRhabdomyosarcoma (RMS), a common soft-tissue malignancy in pediatrics, presents high invasiveness and mortality. However, besides known changes in the PAX3/7-FOXO1 fusion gene in alveolar RMS, the molecular mechanisms of the disease remain incompletely understood. The purpose of the study is to recognize potential biomarkers related with RMS and analyse their molecular mechanism, diagnosis and prognostic significance.MethodsThe Gene Expression Omnibus was used to search the RMS and normal striated muscle data sets. Differentially expressed genes (DEGs) were filtered using R software. The DAVID has become accustomed to performing functional annotations and pathway analysis on DEGs.The protein interaction was constructed and further processed by the STRING tool and Cytoscape software. Kaplan–Meier was used to estimate the effect of hub genes on the ending of sarcoma sufferers, and the expression of these genes in RMS was proved by real-time polymerase chain reaction (RT-PCR). Finally, the expression of CDK1 and CCNB1 in RMS was validated by immunohistochemistry (IHC).ResultsA total of 1932 DEGs were obtained, amongst which 1505 were up-regulated and 427were down-regulated. Up-regulated genes were largely enriched in the cell cycle, ECM-receptor interaction, PI3K/Akt and p53 pathways, whilst down-regulated genes were primarily enriched in the muscle contraction process. CDK1, CCNB1, CDC20, CCNB2, AURKB, MAD2L1, HIST2H2BE, CENPE, KIF2C and PCNA were identified as hub genes by Cytoscape analyses. Survival analysis showed that, except for HIST2H2BE, the other hub genes were highly expressed and related to poor prognosis in sarcoma. RT-PCR validation showed that CDK1, CCNB1, CDC20, CENPE and HIST2H2BE were significantly differential expression in RMS compared to the normal control. IHC revealed that the expression of CDK1 (28/32, 87.5%) and CCNB1 (26/32, 81.25%) were notably higher in RMS than normal controls (1/9, 11.1%; 0/9, 0%). Moreover, the CCNB1 was associated with the age and location of the patient’s onset.ConclusionsThese results show that these hub genes, especially CDK1 and CCNB1, may be potential diagnostic biomarkers for RMS and provide a new perspective for the pathogenesis of RMS.

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“…It was reported that CDC20 is significantly overexpressed in different cancer types [ 8 ]. In order to better understand the role of CDC20 in cancer, we obtained RNA-Seq-based CDC20 expression levels in 33 human cancers from The Cancer Genome Atlas (TCGA) rich dataset.…”

Section: Resultsmentioning

confidence: 99%

“…Accumulating evidence indicates that CDC20 plays an important role in the development of human tumors [ 7 ]. CDC20 is overexpressed in a variety of human tumors including colorectal cancer (CRC) [ 8 , 9 ]. For example, CDC20 is overexpressed in both CRC cell lines and primary cancer tissues compared to normal colorectal epithelial cells and paracancerous tissue samples.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of CDC20 Increases Radiosensitivity through Mcl-1/p-Chk1-Mediated DNA Damage and Apoptosis in Tumor Cells

Gao

Wen

Chen

et al. 2020

IJMS

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Radiotherapy is an important modality for the local control of human cancers, but the radioresistance induced by aberrant apoptotic signaling is a hallmark of cancers. Restoring the aberrant apoptotic pathways is an emerging strategy for cancer radiotherapy. In this study, we determined that targeting cell division cycle 20 (CDC20) radiosensitized colorectal cancer (CRC) cells through mitochondrial-dependent apoptotic signaling. CDC20 was overexpressed in CRC cells and upregulated after radiation. Inhibiting CDC20 activities genetically or pharmacologically suppressed the proliferation and increased radiation-induced DNA damage and intrinsic apoptosis in CRC cells. Mechanistically, knockdown of CDC20 suppressed the expression of antiapoptotic protein Mcl-1 but not other Bcl-2 family proteins. The expressions of CDC20 and Mcl-1 respond to radiation simultaneously through direct interaction, as evidenced by immunoprecipitation and glutathione S-transferase (GST) pull-down assays. Subsequently, decreased Mcl-1 expression inhibited the expression level of phosphorylated checkpoint kinase 1 (p-Chk1), thereby resulting in impaired DNA damage repair through downregulating the homologous recombination repair protein Rad51 and finally causing apoptotic signaling. In addition, both CDC20 and Chk1 inhibitors together, through in vivo studies, confirmed the radiosensitizing effect of CDC20 via inhibiting Mcl-1 and p-Chk1 expression. In summary, our results indicate that targeting CDC20 is a promising strategy to improve cancer radiotherapy.

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CDC20 overexpression leads to poor prognosis in solid tumors

Cited by 15 publications

References 21 publications

Identification of Potential Crucial Genes Associated With the Pathogenesis and Prognosis of Endometrial Cancer

Identification of Potential Crucial Genes Associated With the Pathogenesis and Prognosis of Endometrial Cancer

CDK1 and CCNB1 as potential diagnostic markers of rhabdomyosarcoma: validation following bioinformatics analysis

Downregulation of CDC20 Increases Radiosensitivity through Mcl-1/p-Chk1-Mediated DNA Damage and Apoptosis in Tumor Cells

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