Expression of CDC20 in lung adenocarcinoma tissues and its effect on the proliferation and invasion of lung adenocarcinoma cells

Xueqin ZHOU; Yanchao LUAN; Li ZHAO; Chaochao RONG; Na YANG

doi:10.19401/j.cnki.1007-3639.2024.05.003

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Expression of CDC20 in lung adenocarcinoma tissues and its effect on the proliferation and invasion of lung adenocarcinoma cells

Article | 更新时间：2025-12-31

- Expression of CDC20 in lung adenocarcinoma tissues and its effect on the proliferation and invasion of lung adenocarcinoma cells
- China Oncology Vol. 34, Issue 5, Pages: 460-472(2024)
- 作者机构：
  
  河北省胸科医院胸外科，河北省肺病重点实验室，河北石家庄 050001
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.05.003
  CLC： R734.2
- Received：17 November 2023，
  
  Revised：2024-04-22，
  
  Published：30 May 2024
- 稿件说明：
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Xueqin ZHOU, Yanchao LUAN, Li ZHAO, et al. Expression of CDC20 in lung adenocarcinoma tissues and its effect on the proliferation and invasion of lung adenocarcinoma cells[J]. China Oncology, 2024, 34(5): 460-472.
DOI：

Xueqin ZHOU, Yanchao LUAN, Li ZHAO, et al. Expression of CDC20 in lung adenocarcinoma tissues and its effect on the proliferation and invasion of lung adenocarcinoma cells[J]. China Oncology, 2024, 34(5): 460-472. DOI： 10.19401/j.cnki.1007-3639.2024.05.003.

摘要

背景与目的：

肺腺癌具有早期发现难、肿瘤进展快及晚期手术切除率低等特点。尽管单药免疫治疗和免疫治疗联合化疗的相关研究在改善预后、克服耐药方面已初显成效，但是大部分肺腺癌患者从中获益仍有限。因此，迫切需要寻找具有相对较高灵敏度和特异度的新型生物标志物，以改善肺腺癌患者的预后。细胞分裂周期蛋白20（cell division cycle protein 20，CDC20）参与多种肿瘤的发生、发展，但在肺腺癌中的生物学作用及机制尚未明确。本研究旨在探究CDC20在肺腺癌中的表达情况及其对肺腺癌患者预后的预测价值，并分析CDC20对肺腺癌细

胞增殖和侵袭能力的影响。

方法：

采用免疫组织化学（immunohistochemistry，IHC）检测CDC20在肺腺癌中的表达情况并结合生物信息学和临床病理学参数分析其与预后不良的相关性。采用Kaplan-Meier生存曲线描述CDC20对肺腺癌患者术后生存率的影响，采用COX多因素回归分析影响肺腺癌患者术后生存率的独立预后因素。通过受试者工作特征曲线分析CDC20表达在肺腺癌患者中的诊断价值。采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）和蛋白质印迹法（Western blot）检测人正常肺上皮细胞系BEAS-2B、人肺腺癌细胞系A549和H1299中CDC20的表达水平。细胞实验中，通过敲低肺腺癌细胞中的CDC20，分为si-NC（对照组）、si-CDC20#1（敲低组1）和si-CDC20#2（敲低组2）3个组。采用细胞计数试剂盒-8（cell counting kit-8，CCK-8）、克隆形成、transwell和划痕实验检测细胞增殖、迁移和侵袭能力。通过基因本体论（Gene Ontology，GO）功能和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析CDC20在肺腺癌中的生物学作用。通过基因集富集分析（gene set enrichment analysis，GSEA）CDC20在肺腺癌中可能的调控通路。本研究经河北省胸科医院伦理委员会批准（编号：2022051）。

结果：

生物信息学及IHC结果均显示，CDC20在肺腺癌组织中显著高表达（

0.05）。生物信息学与临床参数分析结果均显示，CDC20高表达与患者预后不良相关。Kaplan-Meier生存分析和COX回归分析均显示，CDC20表达情况与患者术后生存率呈显著负相关（

0.05）。敲低CDC20能抑制肺腺癌细胞增殖、迁移和侵袭（

0.05）。GO功能、KEGG通路和GSEA结果均显示，CDC20与细胞周期相关。

结论：

CDC20在肺腺癌中高表达，CDC20高表达是肺腺癌患者不良预后的独立危险因素。CDC20能促进肺腺癌细胞增殖、迁移和侵袭。

Abstract

Background and purpose:

Lung adenocarcinoma has the characteristics of difficult early detection

rapid tumor progression and low surgical resection rate. Although studies on immunotherapy alone and immunotherapy combined with chemotherapy have shown initial success in improving prognosis and overcoming drug resistance

the majority of lung adenocarcinoma patients still receive limited benefits. Therefore

there is an urgent need to identify novel biomarkers with relatively high sensitivity and specificity to improve the prognosis of lung adenocarcinoma. Cell division cycle protein 20 (CDC20) is involved in the occurrence and development of various tumors

but its biological role and mechanism in lung adenocarcinoma remain unclear. The aim of this study was to investigate the expression of CDC20 in lung adenocarcinoma and its predictive value for the progno

sis of patients with lung adenocarcinoma

and to further explore the effects of CDC20 on the proliferation and invasion capabilities of lung adenocarcinoma cells.

Methods:

Utilizing immunohistochemistry (IHC) to detect the expression of CDC20 in lung adenocarcinoma tissues

we analyzed its correlation with poor prognosis in combination with bioinformatics and clinicopathological parameters. Kaplan-Meier survival curves were employed to illustrate the impact of CDC20 on postoperative survival rates in lung adenocarcinoma patients. COX multivariate regression analysis was conducted to identify independent prognostic factors influencing postoperative survival rates. Additionally

receiver operating characteristic (ROC) curves were applied to assess the diagnostic value of CDC20 expression in lung adenocarcinoma patients. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot were used to measure the expression levels of CDC20 in normal human lung epithelial cells (BEAS-2B) and human lung adenocarcinoma cells (A549 and H1299). In cellular experiments

CDC20 was knocked down in lung adenocarcinoma cells

which were divided into three groups: si-NC (control group)

si-CDC20#1 (knockdown group 1) and si-CDC20#2 (knockdown group 2). Cell counting kit-8 (CCK-8)

colony formation

transwell and wound healing assays were conducted to assess cell proliferation

migration and invasion capabilities. Functional enrichment analysis using Geng Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was conducted to explore the biological roles of CDC20 in lung adenocarcinoma. Finally

gene set enrichment analysis (GSEA) was employed to investigate potential regulatory pathways of CDC20 in lung adenocarcinoma. This study was approved by the Ethics Committee of Hebei Chest Hospital (Number: 2022051).

Results:

The results of both bioinformatics analysis and IHC demonstrated a significantly high expression of CDC20 in lung adenocarcinoma tissues (

0.05). Both bioinformatics analysis and clinical parameter evaluation revealed a correlation between high CDC20 expression and poor patient prognosis. Kaplan-Meier survival analysis and COX regression analysis consistently indicated a significant negative correlation between CDC20 expression and postoperative survival rates in patients (

0.05). Additionally

the expression levels of CDC20 were higher in human lung adenocarcinoma cell lines A549 and H1299 compared with BEAS-2B (

0.05). Knockdown of CDC20 effectively inhibited the proliferation

migration and invasion of lung adenocarcinoma cells (

0.05). The results of GO

KEGG pathways and GSEA consistently pointed to a relationship between CDC20 and cell cycle regulation.

Conclusion:

CDC20 is highly expressed in lung adenocarcinoma. High expression of CDC20 is an independent risk factor for poor prognosis of lung adenocarcinoma patient. CDC20 can promote the proliferation

migration and invasion of lung adenocarcinoma cells.

关键词

Keywords

references

SIEGEL R L , MILLER K D , JEMAL A . Cancer statistics, 2016 [J ] . CA Cancer J Clin , 2016 , 66 ( 1 ): 7 - 30 .

CASCONE T , FRADETTE J , PRADHAN M , et al. Tumor immunology and immunotherapy of non-small cell lung cancer [J ] . Cold Spring Harb Perspect Med , 2022 , 12 ( 5 ): a037895.

CHEN P X , LIU Y H , WEN Y K , et al. Non-small cell lung cancer in China [J ] . Cancer Commun , 2022 , 42 ( 10 ): 937 - 970 .

SINGH S S , DAHAL A , SHRESTHA L , et al. Genotype driven therapy for non-small cell lung cancer: resistance, pan inhibitors and immunotherapy [J ] . Curr Med Chem , 2020 , 27 ( 32 ): 5274 - 5316 . DOI: 10.2174/0929867326666190222183219 http://doi.org/10.2174/0929867326666190222183219

CHENG S J , CASTILLO V , SLIVA D . CDC20 associated with cancer metastasis and novel mushroom-derived CDC20 inhibitors with antimetastatic activity [J ] . Int J Oncol , 2019 , 54 ( 6 ): 2250 - 2256 .

CHI J J , LI H C , ZHOU Z , et al. A novel strategy to block mitotic progression for targeted therapy [J ] . EBioMedicine , 2019 , 49 : 40 - 54 . DOI: S2352-3964(19)30677-2 http://doi.org/S2352-3964(19)30677-2

WANG J J , ZHOU F G , LI Y , et al. Cdc20 overexpression is involved in temozolomide-resistant glioma cells with epithelial-mesenchymal transition [J ] . Cell Cycle , 2017 , 16 ( 24 ): 2355 - 2365 . DOI: 10.1080/15384101.2017.1388972 http://doi.org/10.1080/15384101.2017.1388972

MA X , ZHOU L , ZHENG S S . Transcriptome analysis revealed key prognostic genes and microRNAs in hepatocellular carcinoma [J ] . PeerJ , 2020 , 8 : e8930 .

LOVE M I , HUBER W , ANDERS S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 [J ] . Genome Biol , 2014 , 15 ( 12 ): 550.

LIU J F , LICHTENBERG T , HOADLEY K A , et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics [J ] . Cell , 2018 , 173 ( 2 ): 400 - 416 .e11. DOI: S0092-8674(18)30229-0 http://doi.org/S0092-8674(18)30229-0

YU G C , WANG L G , HAN Y Y , et al. clusterProfiler: an R package for comparing biological themes among gene clusters [J ] . OMICS , 2012 , 16 ( 5 ): 284 - 287 . DOI: 10.1089/omi.2011.0118 http://doi.org/10.1089/omi.2011.0118

GIOPANOU I , KANELLAKIS N I , GIANNOU A D , et al. Osteopontin drives KRAS -mutant lung adenocarcinoma [J ] . Carcinogenesis , 2020 , 41 ( 8 ): 1134 - 1144 .

贾利晴 , 葛小路 , 姜琳 , 等 . LncRNA PKD2-2-3对肺腺癌细胞增殖、克隆形成、迁移及侵袭能力的影响 [J ] . 中国癌症杂志 , 2023 , 33 ( 8 ): 717 - 725 . DOI: 10.19401/j.cnki.1007-3639.2023.08.001 http://doi.org/10.19401/j.cnki.1007-3639.2023.08.001

JIA L Q , GE X L , JIANG L , et al. The impact of lncRNA PKD2-2-3 on the proliferation, colony formation, migration, and invasion abilities of lung adenocarcinoma cells [J ] . China Oncol , 2023 , 33 ( 8 ): 717 - 725 .

WU Q W , YU L L , LIN X Q , et al. Combination of serum miRNAs with serum exosomal miRNAs in early diagnosis for non-small-cell lung cancer [J ] . Cancer Manag Res , 2020 , 12 : 485 - 495 . DOI: 10.2147/CMAR.S232383 http://doi.org/10.2147/CMAR.S232383

刘晓丽 , 柴文君 , 孙磊 , 等 . 肺腺癌中可变剪接调控因子KHSRP调控的差异剪接基因分析 [J ] . 中国癌症杂志 , 2023 , 33 ( 07 ): 637 - 645 .

LIU X L , CHAI W J , SUN L , et al. Analysis of differentially spliced genes regulated by the alternative splicing factor KHSRP in lung adenocarcinoma [J ] . China Oncol , 2023 , 33 ( 7 ): 637 - 645 .

CUADRADO M , GARZÓN J , MORENO S , et al. Efficient terminal erythroid differentiation requires the APC/C cofactor Cdh1 to limit replicative stress in erythroblasts [J ] . Sci Rep , 2022 , 12 ( 1 ): 10489 . DOI: 10.1038/s41598-022-14331-6 http://doi.org/10.1038/s41598-022-14331-6

KIM J H , PATEL R . Mad2B forms a complex with Cdc20, Cdc27, Rev3 and Rev1 in response to cisplatin-induced DNA damage [J ] . Korean J Physiol Pharmacol , 2023 , 27 ( 5 ): 427 - 436 .

ZHANG Y , XUE Y B , LI H , et al. Inhibition of cell survival by curcumin is associated with downregulation of cell division cycle 20 (Cdc20) in pancreatic cancer cells [J ] . Nutrients , 2017 , 9 ( 2 ): 109.

PARMAR M B , K C R B , LÖBENBERG R , et al. Additive polyplexes to undertake siRNA therapy against CDC20 and survivin in breast cancer cells [J ] . Biomacromolecules , 2018 , 19 ( 11 ): 4193 - 4206 . DOI: 10.1021/acs.biomac.8b00918 http://doi.org/10.1021/acs.biomac.8b00918

LI K , MAO Y H , LU L , et al. Silencing of CDC20 suppresses metastatic castration-resistant prostate cancer growth and enhances chemosensitivity to docetaxel [J ] . Int J Oncol , 2016 , 49 ( 4 ): 1679 - 1685 . DOI: 10.3892/ijo.2016.3671 http://doi.org/10.3892/ijo.2016.3671

LI J X , WANG Y C , WANG X , et al. CDK1 and CDC20 overexpression in patients with colorectal cancer are associated with poor prognosis: evidence from integrated bioinformatics analysis [J ] . World J Surg Oncol , 2020 , 18 ( 1 ): 50.

YANG G , WANG G , XIONG Y F , et al. CDC20 promotes the progression of hepatocellular carcinoma by regulating epithelial-mesenchymal transition [J ] . Mol Med Rep , 2021 , 24 ( 1 ): 483.

ZHANG Y Q , LI J Y , YI K K , et al. Elevated signature of a gene module coexpressed with CDC20 marks genomic instability in glioma [J ] . Proc Natl Acad Sci U S A , 2019 , 116 ( 14 ): 6975 - 6984 .

WANG L X , ZHANG J F , WAN L X , et al. Targeting CDC20 as a novel cancer therapeutic strategy [J ] . Pharmacol Ther , 2015 , 151 : 141 - 151 .

WANG L X , YANG C L , CHU M , et al. Cdc20 induces the radioresistance of bladder cancer cells by targeting FoxO1 degradation [J ] . Cancer Lett , 2021 , 500 : 172 - 181 . DOI: 10.1016/j.canlet.2020.11.052 http://doi.org/10.1016/j.canlet.2020.11.052

CHEN Z H , JING Y J , YU J B , et al. ESRP1 induces cervical cancer cell G1-phase arrest via regulating cyclin A2 mRNA stability [J ] . Int J Mol Sci , 2019 , 20 ( 15 ): 3705.

AMADOR V , GE S , SANTAMARÍA P G , et al. APC/C (CDC20) controls the ubiquitin-mediated degradation of p21 in prometaphase [J ] . Mol Cell , 2007 , 27 ( 3 ): 462 - 473 .

ZHENG Y C , SHI Y , YU S , et al. GTSE1, CDC20, PCNA, and MCM6 synergistically affect regulations in cell cycle and indicate poor prognosis in liver cancer [J ] . Anal Cell Pathol , 2019 , 2019 : 1038069 .

KAPANIDOU M , CURTIS N L , BOLANOS-GARCIA V M . CDC20: at the crossroads between chromosome segregation and mitotic exit [J ] . Trends Biochem Sci , 2017 , 42 ( 3 ): 193 - 205 . DOI: S0968-0004(16)30209-2 http://doi.org/S0968-0004(16)30209-2

CHU Z W , ZHANG X Y , LI Q Y , et al. CDC20 contributes to the development of human cutaneous squamous cell carcinoma through the Wnt/β-catenin signaling pathway [J ] . Int J Oncol , 2019 , 54 ( 5 ): 1534 - 1544 .

LI J , KARKI A , HODGES K B , et al. Cotargeting polo-like kinase 1 and the Wnt/β-catenin signaling pathway in castration-resistant prostate cancer [J ] . Mol Cell Biol , 2015 , 35 ( 24 ): 4185 - 4198 . DOI: 10.1128/MCB.00825-15 http://doi.org/10.1128/MCB.00825-15

KONG J J , WANG X T , WANG J L , et al. Silencing of RAB42 down-regulated PD-L1 expression to inhibit the immune escape of hepatocellular carcinoma cells through inhibiting the E2F signaling pathway [J ] . Cell Signal , 2023 , 108 : 110692 .

ZHANG Y , LYU L , WANG W , et al. High expression of E2F transcription factors 7: an independent predictor of poor prognosis in patients with lung adenocarcinoma [J ] . Medicine , 2022 , 101 ( 33 ): e29253.

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