FISH Analysis of TOP2A and HER-2 Aberrations in Female Breast Carcinoma on Archived Material: Egyptian NCI Experience

Badawy, Omnia M.; Loay, Iman

doi:10.1097/pai.0000000000000574

Cited by 10 publications

(7 citation statements)

References 29 publications

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“…As a DNA replication-and cell division-regulating enzyme, TOP2A is the main target of several anticancer drugs, such as doxorubicin, etoposide, and mitoxantrone (50). High expression levels of TOP2A in various types of tumors, such as lung adenocarcinoma, bladder urothelial carcinoma, breast, prostate and colon cancer, indicates a poor prognosis (51)(52)(53)(54)(55), although this has not been previously reported in HCC. However, Panvichian et al (56) have demonstrated that the high expression of TOP2A in HCC is associated with the high expression of Ki67, and Ki-67 expression has been found to correlate with tumor growth rate and poor prognosis in HCC (57), which indicates that TOP2A is a potential target for the treatment of HCC.…”

Section: Discussionmentioning

confidence: 99%

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

et al. 2020

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Hepatocellular carcinoma (HCC) is a common malignant tumor in the clinic. Although there are increasing numbers of available treatment methods, their therapeutic effects are not satisfactory. The clinical indicators commonly used to predict the prognosis of HCC include tumor size, degree of cirrhosis, degree of tumor differentiation and tumor microvascular invasion; however, there are currently no molecular indicators that can predict the prognosis of HCC. Due to the differences in the progression of liver cancer among individuals, there is a growing need for prognostic biomarkers to accurately stratify patients for appropriate risk-adaptive treatment. The DNA topoisomerase 2-α (TOP2A) gene, which is located on human chromosome 17, encodes DNA topoisomerase IIα. Previous studies have demonstrated that TOP2A indicates a poor prognosis in patients with various types of tumors, but no such studies are currently available on HCC. By analyzing the differential expression of TOP2A in 50 pairs of tumor and paracancerous tissue samples in The Cancer Genome Atlas (TCGA) database, the present study revealed that the expression of TOP2A was significantly higher in tumor tissue compared with that in paracancerous tissue (P=6.319x10-16). In the collected clinical samples, the mRNA expression levels of TOP2A were significantly upregulated in HCC tumor tissues compared with those in the paracancerous tissues (P=6.40x10-3), suggesting that TOP2A was associated with the occurrence and development of liver cancer. In addition, the associations between TOP2A expression, clinicopathological features and prognosis were analyzed using a multi-center large sample dataset from TCGA database, and the results demonstrated that high expression of TOP2A was associated with a higher T stage, poorer clinical stage and higher histological grade compared with those in patients with low TOP2A expression. High expression of TOP2A was also identified to be associated with a poor prognosis of HCC, particularly in Asian populations. These results suggested that high expression of TOP2A in HCC tissues may be closely associated with tumor progression and metastasis, which may be used as a biological indicator to predict tumor prognosis in clinical practice.

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Section: Discussionmentioning

confidence: 99%

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

et al. 2020

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“…It seems that as a key regulator of genetic process of cells, neither amplification nor deletion of TOP2A gene benefits the clinical outcome of cancer patients. Results of some investigations could explain these findings: both amplification and deletion of TOP2A gene were associated with polysomy of chromosome 17 50 . Chromosome 17 polysomy was one of the frequent major abnormality events and correlated with aggressive biological behavior of breast cancer 51 , 52 .…”

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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“…TOP2A plays a crucial role in DNA replication, gene expression and other biological behaviours 34 . Higher expression of TOPA2 has been identified in lung cancer, bladder and breast cancer 35–37 . TOP2A was also found to be overexpressed in HCC, leading to a poor prognosis of HCC patients 38 .…”

Section: Discussionmentioning

confidence: 99%

CircADSS contributes to hepatocellular carcinoma development by regulating miR‐431‐5p/TOP2A

Gong

Sun

et al. 2023

Clin Exp Pharma Physio

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CircRNAs participated in regulating hepatocellular carcinoma (HCC), and the regulation function of circRNA adenylosuccinate synthase (circADSS) on HCC development is not clear. RT-qPCR and western blot were performed to detect RNA expression.Cell proliferation was analysed by CCK-8 and EdU assay. Cell cycle distribution was analysed by flow cytometry assay. Cell migration and invasion were measured by transwell assay. Mechanism assays were employed to examine the interaction between miR-431-5p and circADSS, or TOP2A. Xenograft mouse model was constructed for in vivo assay. CircADSS and TOP2A expression were boosted, while miR-431-5p was limited in tumour tissues and cells. CircADSS silencing decreased HCC cell proliferation, cell cycle progression, migration, invasion, as well as EMT.MiR-431-5p inhibitors or ectopic TOP2A expression could restore the effect of cir-cADSS knockdown on HCC progression. There was target relationship between miR-431-5p and circADSS, or TOP2A. Knockdown of circADSS suppressed tumour growth in vivo. CircADSS could regulate HCC cell malignancy by miR-431-5p/TOP2A axis.

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FISH Analysis of TOP2A and HER-2 Aberrations in Female Breast Carcinoma on Archived Material: Egyptian NCI Experience

Cited by 10 publications

References 29 publications

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

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

CircADSS contributes to hepatocellular carcinoma development by regulating miR‐431‐5p/TOP2A

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