Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer

Chen, Jim-Ray; Chien, Hui‐Ping; Chen, Kuo-Su; Hwang, Cheng‐Cheng; Chen, Huang-Yang; Yeh, Kun-Yan; Hsieh, Tsan-Yu; Chang, Liang‐Che; Hsu, Yuan-Chun; Lu, Renjie; Hua, Chung-Ching

doi:10.1097/md.0000000000005582

Cited by 15 publications

(13 citation statements)

References 35 publications

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“…Yang et al demonstrated that PBK promotes the metastasis of hepatocellular carcinoma by activating the ETV4-uPAR signaling pathway 40 . In addition, TOP2A contributes to the early detection and targeted therapy of a variety of cancers [41][42][43] , including HCC 44 . However, the relationship between some of these genes, such as NEK2, and HCC remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis

Zhou

Hao

et al. 2019

Cell Transplant

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Hepatocellular carcinoma (HCC) is a widespread, common type of cancer in Asian countries, and the need for biomarker-matched molecularly targeted therapy for HCC has been increasingly recognized. However, the effective treatment for HCC is unclear. Therefore, identifying additional hub genes and pathways as novel prognostic biomarkers for HCC is necessary. In this study, the expression profiles of GSE121248, GSE45267 and GSE84402 were obtained from the Gene Expression Omnibus (GEO), including 132 HCC and 90 noncancerous liver tissues. Differentially expressed genes (DEGs) between HCC and noncancerous samples were identified by GEO2 R and Venn diagrams. In total, 109 DEGs were identified in these datasets, including 24 upregulated genes and 85 downregulated genes. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) preliminary analyses of the DEGs were performed using DAVID. The protein–protein interaction (PPI) network of the DEGs was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized in Cytoscape. Module analysis of the PPI network was performed using MCODE to get hub genes. Moreover, the influence of the hub genes on overall survival was determined with Kaplan–Meier plotter. All hub genes were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and KEGG. Overall, the hub genes DTL, CDK1, CCNB1, RACGAP1, ECT2, NEK2, BUB1B, PBK, TOP2A, ASPM, HMMR, RRM2, CDKN3, PRC1, and ANLN were upregulated in HCC, and the survival rate was lower for HCC with increased expression of these hub genes. CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway, and CCNB1, CDK1, and BUB1B were enriched in the cell cycle. In brief, we screened 15 hub genes and pathways to identify potential prognostic markers for HCC treatment. However, the specific occurrence and development of HCC with expression of the hub genes should be verified in vivo and in vitro.

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Section: Discussionmentioning

confidence: 99%

Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis

Zhou

Hao

et al. 2019

Cell Transplant

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“…All the included literatures were published in English. Twelve articles 11 - 13 , 23 - 29 , 32 , 38 investigated the association between TOP2A expression and the prognosis of malignant tumor for HR; thirteen articles 8 , 13 , 16 , 17 , 28 , 30 , 31 , 33 - 37 , 40 researched the relationship between the amplification of TOP2A gene and the cancer prognosis for HR; four articles 34 , 39 - 41 studied the association between the alteration of TOP2A gene and the prognosis of cancer for HR. The types of cancers covered breast cancer, endometrial cancer, adrenocortical cancer, of which breast cancer accounts for the vast majority.…”

Section: Resultsmentioning

confidence: 99%

“…The findings that TOP2A amplification predicted longer overall survival in Australia might due to the different background of ethnicity. One study performed in Taiwanese invasive female breast cancers by tissue microarrays suggested no prognostic value of TOP2A amplification 32 . Besides, studies have indicated potential of TOP2A amplification as a useful clinical biomarker of sensitivity to adjuvant anthracycline-based chemotherapy in patients with breast cancers pertaining to the HER2 positive subgroup in British 16 .…”

Section: Discussionmentioning

confidence: 99%

Copy number variation and high expression of DNA topoisomerase II alpha predict worse prognosis of cancer: a meta-analysis

et al. 2018

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Background: Increasing numbers of literatures have investigated the association between TOP2A and cancer prognosis. But the results of the relationship between the two were inconclusive. The aim of this meta-analysis was to elucidate whether TOP2A could predict prognosis of cancer.Materials and Methods: A systematically searching for potentially valuable literature was conducted through electronic databases containing PubMed and Web of Science. Hazard Ratio (HR) and their 95% confidence interval (CI) were used to assess the strength of association between TOP2A and cancer prognosis.Results: Finally twenty-five studies were included in this meta-analysis. High expression of TOP2A was associated with shorter disease free survival (DFS) of cancer prognosis compared with low expression of TOP2A (HR= 1.36, 95% CI= 1.18-1.57, P<0.001). Amplification of TOP2A gene showed no significant association with overall survival (OS), disease free survival (DFS) or relapse free survival (RFS) compared with non-amplification of TOP2A (OS: HR= 0.96, 95%CI= 0.75-1.22, P= 0.735; DFS: HR= 0.93, 95%CI= 0.70-1.23, P= 0.621; RFS: HR= 0.97, 95%CI= 0.71-1.34, P= 0.867). In the subgroup of regions, TOP2A amplification was associated with longer overall survival (HR= 0.66, 95%CI= 0.46-0.96, P= 0.029) in Australia. Alteration (amplification or deletion) of TOP2A gene demonstrated shorter survival according to OS and RFS compared with those with normal TOP2A status (OS: HR= 1.37, 95%CI= 1.22-1.55, P<0.001; RFS: HR= 1.26, 95%CI= 1.12-1.41, P<0.001).Conclusion: High TOP2A expression suggested significant relationship with worse cancer prognosis. Alteration (amplification or deletion) of TOP2A gene was also significantly related to shorter survival of cancer patients. Therefore, TOP2A might be used as an indicator for poor prognosis of cancer in the future.

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“…A most well-known cancer associated with TOP2A is breast cancer, in which TOP2A is usually simultaneously deleted or overexpressed with ERBB2 (erb-b2 receptor tyrosine kinase 2), thus the two genes are usually co-tested to guide the usage of Herceptin, an anticancer agent. 21,22 With the help of bioinformatic analysis and immunohistochemistry (IHC) technology, Ma at al. 23 revealed that TOP2A was overexpressed in non-small cell lung cancer (NSCLC) comparing to normal lung tissues, which associated with the worse overall survival in NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

<p>TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling</p>

Bi¹,

Shen²,

Yin³

et al. 2020

CMAR

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Background/Objective: Topoisomerases type IIA (TOP2A) was identified to present with a high-expression pattern in cervical cancer. However, TOP2A role in the progression of cervical cancer remains unknown. Here, we aimed to explore the effect and reveal the underlying mechanism of TOP2A in the migration, invasion and epithelial-mesenchymal transition (EMT) of cervical cancer. Materials and Methods: The expression profiles of TOP2A in 20 paired cervical cancer tissues and the paracancerous normal tissues were detected by using Western blotting assay. Transwell chambers were used to test cell migration and invasion abilities. Cell morphology and the expressions of E-cadherin and N-cadherin were detected to assess cell EMT. LY294002 was used to inhibit the activation of PI3K/AKT signaling. Results: Compared with the paracancerous normal tissues, TOP2A was overexpressed in 85% (17/20) cervical cancer tissues. Repression of TOP2A expression in SiHa cells significantly weakened cell migration and invasion abilities, reduced cell numbers in shuttle shape and increased E-cadherin expression while decreased E-cadherin expression. To the opposite, overexpression of TOP2A in Hela cells induced opposite results. In addition, the expression of p-AKT was increased when TOP2A was overexpressed in Hela cells, and p-AKT expression was decreased when TOP2A was silenced in SiHa cells. Moreover, suppression of the PI3K/AKT signaling with LY294002 treatment apparently rescued TOP2A-mediated promotions in cell migration, invasion and EMT in Hela cells. Conclusion: This study reveals that TOP2A is abnormally overexpressed in cervical cancer tissues, and TOP2A overexpression leads to cell migration, invasion and EMT via activating PI3K/AKT signaling.

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Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer

Abstract: Supplemental Digital Content is available in the text

Cited by 15 publications

References 35 publications

Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis

Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis

Copy number variation and high expression of DNA topoisomerase II alpha predict worse prognosis of cancer: a meta-analysis

<p>TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling</p>

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