Characterization of topoisomerase II α and minichromosome maintenance protein 2 expression in anal carcinoma

Scapulatempo‐Neto, Cristovam; Véo, Carlos Augusto Rodrigues; Fregnani, Josï¿1⁄2 Humberto T.G.; Lorenzi, Adriana Tarlá; Mafra, Allini; Melani, Armando Geraldo Franchini; Loaiza, Edgar Antonio Alemï¿1⁄2n; Rosa, Luciana Albina Reis; Oliveira, Cristina Mendes de; Levi, Josï¿1⁄2 Eduardo; Longatto‐Filho, Adhemar

doi:10.3892/ol.2017.5650

Cited by 8 publications

(14 citation statements)

References 28 publications

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“…In addition, TOP2A may be used as an immunohistochemical biomarker for CC (39). Several studies have confirmed the use of TOP2A as a sensitive biomarker for the screening of carcinoma tissues (39,44,45). TOP2A was also frequently overexpressed in several types of cancer, including lung (46), prostate (47), breast (42,48), hepatic (49) and ovarian cancer (50), and glioma (51).…”

Section: Discussionmentioning

confidence: 98%

Bioinformatics analysis shows that TOP2A functions as a key candidate gene in the progression of cervical cancer

Zhao

Zhu

et al. 2020

Biomed Rep

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Cervical cancer (CC) is one of the most prevalent types of cancer affecting females worldwide. However, the molecular mechanisms underlying the development and progression of CC remains to be elucidated. Taking the high incidence and mortality rates amongst women into consideration, the identification of novel biomarkers to prevent CC is of great significance and required to improve diagnosis. Using three raw microarray datasets from the Gene Expression Omnibus database, 188 differentially expressed genes (DEGs) were identified. Gene Ontology and pathway analyses were performed on the DEGs. Through protein-protein interaction network construction and module analysis, eight hub genes [cell division cycle 6, cyclin-dependent kinase 1 (CDK1), cell division control protein 45, budding uninhibited by benzimidazoles 1 (BUB1), DNA topoisomerase II α (TOP2A) and minichromosome maintenance complex component 4, CCNB2 and CCNB1] were identified, but only TOP2A was considered a prognostic factor in survival analysis. There were strong positive correlations between TOP2A and BUB1 (P<0.0001, rs= 0.635), CDK1 (P<0.0001, rs= 0.511), centromere protein F (CENPF) (P<0.0001, rs= 0.677), Rac GTPase activating protein 1 (RACGAP1) (P<0.0001, rs= 0.612), F-box protein 5 (FBXO5) (P<0.0001, rs=0.585) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) (P<0.0001, rs= 0.584). Additionally, BUB1, CDK1, CENPF, RACGAP1, FBXO5 and BUB1B are all potentially suitable candidate targets for the diagnosis and treatment of CC. In conclusion, the present study identified TOP2A as a potential tumor oncogene and a biomarker for the prognosis of CC.

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Section: Discussionmentioning

confidence: 98%

Bioinformatics analysis shows that TOP2A functions as a key candidate gene in the progression of cervical cancer

Zhao

Zhu

et al. 2020

Biomed Rep

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“…Clinical data of the patients was obtained, and is summarized in Table I. HPV16 and HPV18 status, and immunohistochemical analysis of β-globin, p16, antigen Ki67 (Ki67), minichromosome maintenance protein complex (MCM) and DNA topoisomerase 2-α (TOP2A) were retrieved from a previous study (16).…”

Section: Methodsmentioning

confidence: 99%

“…Continued. As described in Scapulatempo-Neto et al (16). HSIL, high-grade squamous intra-epithelial lesion; ADC, adenocarcinoma; SCC, squamous cell carcinoma; F, female; M, male; HPV, human papillomavirus;…”

Section: Methodsmentioning

confidence: 99%

Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors

Bidinotto

Véo

Loaiza

et al. 2016

Molecular Medicine Reports

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Anal cancer is a rare type of digestive tract disease, which has had a crescent incidence in a number of regions. Carcinomas are most frequently found, with squamous cell carcinoma (SCC) comprising ~95% of all anal tumors. The major risk factor for development of this type of tumor is human papillomavirus (HPV) infection. However, previous studies have identified patients with anal cancer that are HPV‑/p16‑and observed that they have a poorer outcome compared with HPV+/p16+ patients. This suggests that molecular profile may drive anal cancer progression. The aim of the present study was to evaluate the mutational status of two important oncogenes, KRAS and BRAF, in a series of anal cancer lesions. Resected tumors of the anal canal (n=43) were evaluated, nine of these were high‑grade squamous intra‑epithelial lesion cases (HSIL), 11 were adenocarcinomas, and 23 SCCs. Direct sequencing of KRAS proto‑oncogene, GTPase (KRAS; codons 12 and 13) and B‑Raf proto‑oncogene, serine/threonine kinase (BRAF; codon 600) was performed and associated with patient clinicopathological and molecular features. There was a trend of poorer prognosis of adenocarcinoma compared with HSIL and SCC. Analysis indicated one SCC patient (2.3%) exhibited a KRAS p.G13D mutation, and one adenocarcinoma patient (2.3%) exhibited a BRAF p.V600E mutation. It was observed that, these mutations are rare in anal tumors, and certain patients may be at a disadvantage using targeted therapies based on KRAS and BRAF mutational status. As there is a low mutation percentage in SCCs, adenocarcinomas and HSIL, there may exist other underlying molecular alterations that result in anal cancer development, which require further elucidation.

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“…The mean age of the patients was 55.9 years (range, 27-86 years). KRAS and BRAF mutation status data were retrieved from our previous study (24), while HPV16 and HPV18 status, and β-globin, p16, Ki-67, minichromosome maintenance protein complex (MCM) and topoisomerase II α (TOP2A) expression immunohistochemical analyses were retrieved from another previous study (25) and are summarized in Table II. All patients included in the present study provided written informed consent, and the study was approved by the Barretos Cancer Hospital Ethical Committee (Barretos, SP, Brazil) approval under the protocol number 310/2010.…”

Section: Methodsmentioning

confidence: 99%

Loss of Raf kinase inhibitor protein expression is associated with human papillomavirus 16 infection in anal tumors

Bidinotto¹,

Véo²,

Loaiza³

et al. 2018

Oncol Lett

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There has been an increase in the incidence of anal cancer in the past two decades, with squamous cell carcinoma (SCC) being the most frequent histological type identified. Among the risk factors, high-risk human papillomavirus (HPV) infection is the most pervasive. Raf kinase inhibitor protein (RKIP) is expressed in a number of normal human tissues and previous studies have demonstrated the prognostic value of the loss of RKIP expression in several gastrointestinal tumors. Therefore, the present study aimed to evaluate the clinical implications of RKIP expression in a series of neoplastic lesions of the anal canal. The resected tumors of 48 patients [8 high-grade intraepithelial lesions (HSILs), 14 adenocarcinomas and 26 squamous cell carcinomas (SCCs)] were immunohistochemically evaluated for RKIP expression, and the results were correlated with clinicopathological data. The results identified a decreased 5-year overall survival rate in patients with adenocarcinoma (40.8%) compared with patients with SCC (76.7%), and a decreased 5-year disease-free survival rate in patients at clinical stages III/IV (37.3 vs. 62.5 and 82.6% for clinical stages 0 and I/II, respectively). Low RKIP expression was revealed in 62.5% of HSILs, 88.5% of SCCs and 100.0% of the adenocarcinomas. High RKIP expression was associated with patient ethnicity (37.5% in non-Caucasians vs. 7.5% in Caucasians) and patient age (33.3% in younger patients vs. 0.0% in older patients). Finally, high RKIP expression was correlated with HPV16 infection status (40% in HPV vs. 5.3% in HPV patients). A correlation was identified between high RKIP expression and lesions with a generally improved prognosis, such as those diagnosed in younger patients, lesions and lesions of lower clinical grades; there was also a negative correlation between high RKIP expression and HPV16 positivity in patients.

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Characterization of topoisomerase II α and minichromosome maintenance protein 2 expression in anal carcinoma

Cited by 8 publications

References 28 publications

Bioinformatics analysis shows that TOP2A functions as a key candidate gene in the progression of cervical cancer

Bioinformatics analysis shows that TOP2A functions as a key candidate gene in the progression of cervical cancer

Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors

Loss of Raf kinase inhibitor protein expression is associated with human papillomavirus 16 infection in anal tumors

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