Overexpression of topoisomerase II alpha protein is a factor for poor prognosis in patients with luminal B breast cancer

Shigematsu, Hideo; Ozaki, Shinji; Yasui, Daisuke; Yamamoto, Hideki; Zaitsu, Junichi; Taniyama, Daiki; Saitou, Akihisa; Kuraoka, Kazuya; Hirata, Taizo; Taniyama, Kiyomi

doi:10.18632/oncotarget.25468

Cited by 17 publications

(15 citation statements)

References 39 publications

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“…DNA Topoisomerase II Alpha ( TOP2A ), encoding a DNA topoisomerase, controls topologic states of DNA during transcription. Previous studies reported that overexpression of TOP2A promoted the progression of breast cancer and prostate cancer ( Kirk et al, 2015 ; Shigematsu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Core Genes Related to Progression and Prognosis of Hepatocellular Carcinoma and Small-Molecule Drug Predication

et al. 2021

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BackgroundHepatocellular carcinoma (HCC) is one of the most leading causes of cancer death with a poor prognosis. However, the underlying molecular mechanisms are largely unclear, and effective treatment for it is limited. Using an integrated bioinformatics method, the present study aimed to identify the key candidate prognostic genes that are involved in HCC development and identify small-molecule drugs with treatment potential.Methods and ResultsIn this study, by using three expression profile datasets from Gene Expression Omnibus database, 1,704 differentially expressed genes were identified, including 671 upregulated and 1,033 downregulated genes. Then, weighted co-expression network analysis revealed nine modules are related with pathological stage; turquoise module was the most associated module. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses (KEGG) indicated that these genes were enriched in cell division, cell cycle, and metabolic related pathways. Furthermore, by analyzing the turquoise module, 22 genes were identified as hub genes. Based on HCC data from gene expression profiling interactive analysis (GEPIA) database, nine genes associated with progression and prognosis of HCC were screened, including ANLN, BIRC5, BUB1B, CDC20, CDCA5, CDK1, NCAPG, NEK2, and TOP2A. According to the Human Protein Atlas and the Oncomine database, these genes were highly upregulated in HCC tumor samples. Moreover, multivariate Cox regression analysis showed that the risk score based on the gene expression signature of these nine genes was an independent prognostic factor for overall survival and disease-free survival in HCC patients. In addition, the candidate small-molecule drugs for HCC were identified by the CMap database.ConclusionIn conclusion, the nine key gene signatures related to HCC progression and prognosis were identified and validated. The cell cycle pathway was the core pathway enriched with these key genes. Moreover, several candidate molecule drugs were identified, providing insights into novel therapeutic approaches for HCC.

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Section: Discussionmentioning

confidence: 99%

Identification of Core Genes Related to Progression and Prognosis of Hepatocellular Carcinoma and Small-Molecule Drug Predication

et al. 2021

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“…Previous literature reported that RRM2 promoted tumorigenesis and progression of pancreatic cancer, lung cancer, gastric cancer, ovarian cancer, bladder cancer and other tumors [21–24], TOP2A gene encoded a DNA topoisomerase, it is an ATP-dependent synthetase and hydrolase that plays a key role in cells and plays an important role in many cellular biological processes, such as DNA replication, chromatin condensation, chromosome segregation, and chromosome structure retention. Studies have found that high expression of TOP2A promoted the progression of breast cancer [25, 26]. UBE2C is also known as UbcH10, which is a member of the ubiquitin-coupled enzyme E2 family.…”

Section: Discussionmentioning

confidence: 99%

Identification of 9 key genes and small molecule drugs in clear cell renal cell carcinoma

Luo

Shen

Chen

et al. 2019

Aging

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Clear cell renal cell carcinoma (ccRCC) is a heterogeneous tumor that the underlying molecular mechanisms are largely unclear. This study aimed to elucidate the key candidate genes and pathways in ccRCC by integrated bioinformatics analysis. 1387 differentially expressed genes were identified based on three expression profile datasets, including 673 upregulated genes and 714 downregulated genes. Then we used weighted correlation network analysis to identify 6 modules associated with pathological stage and grade, blue module was the most relevant module. GO and KEGG pathway analyses showed that genes in blue module were enriched in cell cycle and metabolic related pathways. Further, 25 hub genes in blue module were identified as hub genes. Based on GEPIA database, 9 genes were associated with progression and prognosis of ccRCC patients, including PTTG1, RRM2, TOP2A, UHRF1, CEP55, BIRC5, UBE2C, FOXM1 and CDC20. Then multivariate Cox regression showed that the risk score base on 9 key genes signature was a clinically independent prognostic factor for ccRCC patients. Moreover, we screened out several new small molecule drugs that have the potential to treat ccRCC. Few of them were identified as biomarkers in ccRCC. In conclusion, our research identified 9 potential prognostic genes and several candidate small molecule drugs for ccRCC treatment.

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“…Similarly to the observed for ERBB2 , no correlation was found between TOP2α DNA and RNA levels (results in accordance with [51, 52]). In the future, it will be important to quantify TOP2α protein as there are contradictory published works regarding the clinical significance of the TOP2α expression [22, 24, 25, 51, 52].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the gene aberrations, in HBC, the amplification of TOP2α is correlated with the response to anthracycline chemotherapy and a better outcome of the patient’s survival, independently of its protein expression [22, 23]. TOP2α status has several important implications in breast cancer, however standard tools and cut-off values for estimating TOP2α status have not yet been established [24]. In conclusion, the clinical significance of TOP2α in breast cancer has not yet been clarified [22, 24, 25], being a mandatory research area in this field.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of ERBB2 and TOP2α gene status and expression profile in feline mammary tumors: findings and guidelines

Ferreira

Soares

Correia

et al. 2019

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In humans, the ERBB2 gene amplification and overexpression are biomarkers for invasive breast cancer and a therapeutic target. Also, TOP2α gene aberrations predict the response to anthracycline-based adjuvant chemotherapy. Although feline mammary tumors (FMTs) are good models in comparative oncology, scarce data is available regarding the ERBB2 and TOP2α status. In this study, and for the first time, the ERBB2 DNA status and RNA levels of intracellular (ICD) and extracellular (ECD) coding regions were compared with TOP2α gene status and expression profile, in samples of FMTs and disease-free tissues from the same animal. Results showed that ERBB2 and TOP2α gene status are highly correlated (r=0.87, p<0.0001, n=25), with few tumor samples presenting amplification. Also, the majority of the FMTs showed ERBB2 overexpression coupled with TOP2α overexpression (r=0.87, p<0.0001, n=27), being the ERBB2 -ICD and ECD transcripts highly correlated (r=0.97, p<0.0001, n=27). Significant associations were found between TOP2α gene status or ERBB2 and TOP2α RNA levels with several clinicopathological parameters. This work highlights the need of experimental designs for a precise evaluation of ERBB2 and TOP2α gene status and its expression in FMTs, to improve their clinical management and to further validate them as a suitable model for comparative oncology studies.

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Overexpression of topoisomerase II alpha protein is a factor for poor prognosis in patients with luminal B breast cancer

Cited by 17 publications

References 39 publications

Identification of Core Genes Related to Progression and Prognosis of Hepatocellular Carcinoma and Small-Molecule Drug Predication

Identification of Core Genes Related to Progression and Prognosis of Hepatocellular Carcinoma and Small-Molecule Drug Predication

Identification of 9 key genes and small molecule drugs in clear cell renal cell carcinoma

Assessment of ERBB2 and TOP2α gene status and expression profile in feline mammary tumors: findings and guidelines

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