<italic style="font-style: italic">Topoisomerase </italic>Ⅱ<italic style="font-style: italic">α</italic> Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis

Jin Lu; Shaoguang An; Junjie Ma; Yue Yang; Lei Zhang; Peng Yu; Heng Tao; Yunfan Chen; Haoxuan Zhang

doi:10.24920/004006

Your Location：

Home >

Browse articles >

Topoisomerase Ⅱα Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis

Chinese Medical Sciences Journal Vol. 37, Issue 4, Pages: 331-339(2022)

Original article | Updated：2024-04-10

- Topoisomerase Ⅱα Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis
- Affiliations：
  
  1. 1School of Basic Medicine, Bengbu Medical College, Bengbu, Anhui 233030, China
  2. 2Anhui Key Laboratory of Computational Medicine and Intelligent Health, Bengbu Medical College, Bengbu, Anhui 233030, China
  3. 3Clinical Medical College, Bengbu Medical College, Bengbu, Anhui 233030, China
  4. 4Department of Otolaryngology, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui 233030, China
  5. 5Department of Surgical Oncology, Second Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui 233030, China
- Author bio：
  
  * 86-552-3175286, E-mail: 0100197@bbmc.edu.cn
- Funds：
- DOI：10.24920/004006
  CLC：
- Received：22 September 2021，
  
  Accepted：2021-12-10，
  
  Published Online：04 October 2022，
  
  Published：31 December 2022
- Accepted：
Scan QR Code
Jin Lu, Shaoguang An, Junjie Ma, et al. Topoisomerase Ⅱα Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis[J]. Chinese medical sciences journal, 2022, 37(4): 331-339.
DOI：

Jin Lu, Shaoguang An, Junjie Ma, et al. Topoisomerase Ⅱα Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis[J]. Chinese medical sciences journal, 2022, 37(4): 331-339. DOI： 10.24920/004006.

摘要

目的

研究拓扑异构酶Ⅱα(

topoisomerase II α

，

TOP2α

)基因在肝细胞癌（hepatocellular carcinoma，HCC）中的表达及其在预测HCC患者预后中的作用。

方法

我们利用UALCAN、HCCDB、cBioPortal和Enrichr数据库中的HCC相关数据集，分析

TOP2α

及其共表达基因在HCC组织中的表达和突变情况

以及

TOP2α

及其共表达基因的GO功能和KEGG通路富集情况。利用TIMER数据库分析HCC组织中浸润的免疫细胞水平。采过

Kaplan-Meier

分析

TOP2α

及其共同表达基因与浸润的免疫细胞对HCC患者生存的影响。

结果

TOP2α

及其共同表达基因在HCC组织中高表达（

0.001），并与HCC患者的总生存期缩短有关（

0.0001）。

TOP2α

及其共表达基因主要参与细胞有丝分裂和增殖以及细胞周期通路过程（ID：hsa04110，

= 0.001945）。

TOP2α

及其共同表达基因的突变与HCC患者的总生存期（

= 0.0247）和无病生存期（

= 0.0265）的缩短有关。

TOP2α

与HCC肿瘤组织中B细胞（

= 0.459

0.01）、CD8

T细胞（

= 0.312

0.01）、CD4

T细胞（

= 0.370

0.01）、巨噬细胞（

= 0.459

0.01）、中性粒细胞（

= 0.405

0.01）和树突状细胞（

= 0.473

0.01）的浸润量呈正相关。CD8

T细胞的浸润能显著延长HCC患者3年和5年生存期（

均

0.05），而CD4

T细胞的浸润能显著缩短HCC患者的3、5和10年生存期（

均

0.05）。

结论

TOP2α

可能是一种癌基因，与HCC患者预后不良有关，其可能成为预测肝细胞癌患者预后的生物标志物。

Abstract

Objective

To investigate the expression of

topoisomerase

Ⅱ

(

TOP2α

) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients.

Methods

We used HCC-related datasets in UALCAN

HCCDB

and cBioPortal databases to analyze the expression and mutation of

TOP2α

and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of

TOP2α

and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of

TOP2α

and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by

Kaplan-Meier

plotter analysis.

Results

TOP2α

and its co-expression genes were highly expressed in HCC (

0.001) and detrimental to overall survival of HCC patients (

0.001).

TOP2α

and its co-expression genes were mainly involved in cell mitosis and proliferation

and cell cycle pathway (ID: hsa04110

= 0.001945).

TOP2α

and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (

= 0.0247) and disease-free survival (

= 0.0265) of HCC patients. High

TOP2α

expression was positively correlated with the infiltration of B cell (

= 0.459

0.01)

CD8

T cell (

= 0.312

0.01)

CD4

T cell (

= 0.370

0.01)

macrophage (

= 0.459

0.01)

neutrophil (

= 0.405

0.01)

and dendritic cell (

= 0.473

0.01) in HCC. The CD8

T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all

0.05)

and CD4

T cell infiltration significantly shortened the 3-

and 10-year survival of HCC patients (all

0.05).

Conclusion

TOP2α

may be an oncogene

which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.

关键词

Keywords

references

Liang J , Zhu J , Wang M , et al . Evaluation of AGP fucosylation as a marker for hepatocellular carcinoma of three different etiologies . Sci Rep 2019 ; 9 ( 1 ): 11580 . doi: 10.1038/s41598-019-48043-1 https://dx.doi.org/10.1038/s41598-019-48043-1 . DOI: 10.1038/s41598-019-48043-1 http://doi.org/10.1038/s41598-019-48043-1

Skill NJ , Butler J , O’Brien DC , et al . Financial burden of liver transplant vs . resection for hepatocellular carcinoma . Transplant Proc 2019 ; 51 ( 6 ): 1907 - 12 . doi: 10.1016/j.transproceed.2019.04.026 https://dx.doi.org/10.1016/j.transproceed.2019.04.026 . DOI: 10.1016/j.transproceed.2019.04.026 http://doi.org/10.1016/j.transproceed.2019.04.026 https://linkinghub.elsevier.com/retrieve/pii/S0041134519306311 https://linkinghub.elsevier.com/retrieve/pii/S0041134519306311

Ji D , Hu G , Zhang X , et al . Long non-coding RNA DSCAM-AS 1 accelerates the progression of hepatocellular carcinoma via sponging miR-338-3p . Am J Transl Res 2019 ; 11 ( 7 ): 4290 - 302 .

Meyerovich G , Goykhman Y , Nakache R , et al . Resection vs . transplant listing for hepatocellular carcinoma: an intention-to-treat analysis . Transplant Proc 2019 ; 51 ( 6 ): 1867 - 73 . doi: 10.1016/j.transproceed.2019.02.030 https://dx.doi.org/10.1016/j.transproceed.2019.02.030 . DOI: 10.1016/j.transproceed.2019.02.030 http://doi.org/10.1016/j.transproceed.2019.02.030 https://linkinghub.elsevier.com/retrieve/pii/S0041134518312065 https://linkinghub.elsevier.com/retrieve/pii/S0041134518312065

Huang FY , Wong DK , Tsui VW , et al . Targeted genomic profiling identifies frequent deleterious mutations in FAT4 and TP 53 genes in HBV-associated hepatocellular carcinoma . BMC cancer 2019 ; 19 ( 1 ): 789 . doi: 10.1186/s12885-019-6002-9 https://dx.doi.org/10.1186/s12885-019-6002-9 . DOI: 10.1186/s12885-019-6002-9 http://doi.org/10.1186/s12885-019-6002-9 https://doi.org/10.1186/s12885-019-6002-9 https://doi.org/10.1186/s12885-019-6002-9

Rocha FV , Farias RL , Lima MA , et al . Computational studies, design and synthesis of Pd(II)-based complexes: allosteric inhibitors of the human topoisomerase-II α . J Inorg Biochem 2019 ; 199 : 110725 . doi: 10.1016/j.jinorgbio.2019.110725 https://dx.doi.org/10.1016/j.jinorgbio.2019.110725 . DOI: 10.1016/j.jinorgbio.2019.110725 http://doi.org/10.1016/j.jinorgbio.2019.110725 https://linkinghub.elsevier.com/retrieve/pii/S0162013419300819 https://linkinghub.elsevier.com/retrieve/pii/S0162013419300819

Zeng S , Liu A , Dai L , et al . Prognostic value of TOP2A in bladder urothelial carcinoma and potential molecular mechanisms . BMC cancer 2019 ; 19 ( 1 ): 604 . doi: 10.1186/s12885-019-5814-y https://dx.doi.org/10.1186/s12885-019-5814-y . DOI: 10.1186/s12885-019-5814-y http://doi.org/10.1186/s12885-019-5814-y

Nuncia-Cantarero M , Martinez-Canales S , Andrés-Pretel F , et al . Functional transcriptomic annotation and protein-protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer . Breast Cancer Res Treat 2018 ; 168 ( 3 ): 613 - 23 . doi: 10.1007/s10549-017-4652-3 https://dx.doi.org/10.1007/s10549-017-4652-3 . DOI: 10.1007/s10549-017-4652-3 http://doi.org/10.1007/s10549-017-4652-3 https://doi.org/10.1007/s10549-017-4652-3 https://doi.org/10.1007/s10549-017-4652-3

Ghisoni E , Maggiorotto F , Borella F , et al . TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers . J Ovarian Res 2019 ; 12 ( 1 ): 17 . doi: 10.1186/s13048-019-0492-6 https://dx.doi.org/10.1186/s13048-019-0492-6 . DOI: 10.1186/s13048-019-0492-6 http://doi.org/10.1186/s13048-019-0492-6

Connell LC , Harding JJ , Shia J . Combined intrahepatic cholangiocarcinoma and hepatocellular carcinoma . Chin Clin Oncol 2016 ; 5 ( 5 ): 66 . doi: 10.21037/cco.2016.10.02 https://dx.doi.org/10.21037/cco.2016.10.02 . DOI: 10.21037/cco.2016.10.02 http://doi.org/10.21037/cco.2016.10.02

Sun Q , Yao GD , Song XY , et al . Autophagy antagonizes apoptosis induced by flavan enantiomers from Daphne giraldii in hepatic carcinoma cells in vitro . Eur J Med Chem 2017 ; 133 : 1 - 10 . doi: 10.1016/j.ejmech.2017.03.072 https://dx.doi.org/10.1016/j.ejmech.2017.03.072 . DOI: 10.1016/j.ejmech.2017.03.072 http://doi.org/10.1016/j.ejmech.2017.03.072 https://linkinghub.elsevier.com/retrieve/pii/S0223523417302131 https://linkinghub.elsevier.com/retrieve/pii/S0223523417302131

Iwanaga T . Studies on cases of spontaneous regression of cancer in Japan in 2011, and of hepatic carcinoma, lung cancer and pulmonary metastases in the world between 2006 and 2011 . Gan To Kagaku Ryoho 2013 ; 40 ( 11 ): 1475 - 87 .

Zhou Z , Li Y , Hao H , et al . Screening hub genes as prognostic biomarkers of hepatocellular carcinoma by bioinformatics analysis . Cell Transplant 2019 ; 28 (1_supp l ): 76 S- 86 S. doi: 10.1177/0963689719893950 https://dx.doi.org/10.1177/0963689719893950 . DOI: 10.1177/0963689719893950 http://doi.org/10.1177/0963689719893950

Chen JR , Chien HP , Chen KS , et al . Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer . Medicine (Baltimore) 2017 ; 96 ( 2 ): e5582 . doi: 10.1097/MD.0000000000005582 https://dx.doi.org/10.1097/MD.0000000000005582 . DOI: 10.1097/MD.0000000000005582 http://doi.org/10.1097/MD.0000000000005582 https://journals.lww.com/00005792-201701130-00007 https://journals.lww.com/00005792-201701130-00007

Almeida D , Renê Gerhard , Dina Leitão , et al . Topoisomerase II-alfa gene as a predictive marker of response to anthracyclines in breast cancer . Pathol Res Pract 2014 ; 210 ( 10 ): 675 - 9 . doi: 10.1016/j.prp.2014.06.017 https://dx.doi.org/10.1016/j.prp.2014.06.017 . DOI: 10.1016/j.prp.2014.06.017 http://doi.org/10.1016/j.prp.2014.06.017

Dominguezbrauer C , Thu KL , Mason JM , et al . Targeting mitosis in cancer: emerging strategies . Mol Cell 2015 ; 60 ( 4 ): 524 - 36 . doi: 10.1016/j.molcel.2015.11.006 https://dx.doi.org/10.1016/j.molcel.2015.11.006 . DOI: 10.1016/j.molcel.2015.11.006 http://doi.org/10.1016/j.molcel.2015.11.006

Visconti R , Della Monica R , Grieco D . Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword . Clin Cancer Res 2016 ; 35 ( 1 ): 153 . doi: 10.1186/s13046-016-0433-9 https://dx.doi.org/10.1186/s13046-016-0433-9 . DOI: 10.1186/s13046-016-0433-9 http://doi.org/10.1186/s13046-016-0433-9

Kang X , Song C , Du X , et al . PTEN stabilizes TOP2A and regulates the DNA decatenation . Sci Rep 2016 ; 5 ( 1 ): 17873 . doi: 10.1038/srep17873 https://dx.doi.org/10.1038/srep17873 . DOI: 10.1038/srep17873 http://doi.org/10.1038/srep17873 https://doi.org/10.1038/srep17873 https://doi.org/10.1038/srep17873

Guillén S , Prieto L , Jiménez de Ory S , et al . Prognostic factors of a lower CD4/CD 8 ratio in long term viral suppression HIV infected children . PloS One 2019 ; 14 ( 8 ): e02 20552. doi: 10.1371/journal.pone.0220552 https://dx.doi.org/10.1371/journal.pone.0220552 . DOI: 10.1371/journal.pone.0220552 http://doi.org/10.1371/journal.pone.0220552

Schmidt ME . Identification of novel respiratory syncytial virus CD4 and CD8 T cell epitopes in C57BL/6 mice . Immunohorizons 2019 ; 3 ( 1 ): 1 - 12 . doi: 10.4049/immunohorizons.1800056 https://dx.doi.org/10.4049/immunohorizons.1800056 . DOI: 10.4049/immunohorizons.1800056 http://doi.org/10.4049/immunohorizons.1800056

Utama S , Patriawan P . Correlation of CD4/CD8 ratio with carotid intima-media layer thickness in HIV/AIDS patients at Sanglah General Hospital, Bali, Indonesia . Open Access Maced J Med Sci 2019 ; 7 ( 11 ): 1803 - 7 . doi: 10.3889/oamjms.2019.479 https://dx.doi.org/10.3889/oamjms.2019.479 . DOI: 10.3889/oamjms.2019.479 http://doi.org/10.3889/oamjms.2019.479

Views

504

Downloads

CSCD

Alert me when the article has been cited

Submit

Publicity Resources

A Novel Signature Combing Cuproptosis- and Ferroptosis-Related Genes in Nonalcoholic Fatty Liver Disease

Influence of Gut Microbiota and its Metabolites on Progression of Metabolic Associated Fatty Liver Disease

Multi-Omics and Its Clinical Application in Hepatocellular Carcinoma: Current Progress and Future Opportunities

Research Progress in Targeted Therapy of Hepatocellular Carcinoma

Identification of Potential Therapeutic Targets of Alzheimer’s Disease By Weighted Gene Co-Expression Network Analysis

Related Author

Shou-Zhu Xu

Jing Zhao

Qi-Fan Yang

Rou-Rou Fang

Hai-Lian Lin

Xue-Feng Yang

La-Mei Zhu

Yuan-Yuan Wang

Related Institution

Shaanxi Key Laboratory of Acupuncture & Medicine, Shaanxi University of Chinese Medicine

School of Public Health

Department of Gastroenterology, Affiliated Nanhua Hospital, Hengyang Medical School & University of South China

Hunan Provincial Clinical Research Center for Metabolic Associated Fatty Liver Disease, Affiliated Nanhua Hospital, Hengyang Medical School & University of South China

Department of Hepatobiliary Surgery, Affiliated Nanhua Hospital, Hengyang Medical School & University of South China

⁰

Topoisomerase Ⅱα Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis

DOI：10.24920/004006

摘要

Abstract

关键词

Keywords

references