Topo2A as a prognostic biomarker for patients with resectable esophageal squamous cell carcinomas

Xu, Xiaoling; Zheng, Weihui; Fu, Zhixuan; Li, Zhupeng; Xie, Huaxia; Li, Xianxing; Jiang, Liehao; Wang, Yin; Zhu, Shuang-Mei; Mao, Weimin

doi:10.1007/s12032-014-0396-7

Cited by 11 publications

(5 citation statements)

References 33 publications

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“…TOPO2A is expressed in 48.7% of EC tumors with 24.14% of EC tumors being pathologically considered overexpressed (88). TOPO2A has also been deemed a prognostic factor in EC patients as tumors with no TOPO2A expression survived almost a year longer than patients with low to high TOPO2A expression (89). Also, TOPO2A expression in esophageal tumors has been associated with worse cellular differentiation and more perineural invasion—illuminating a potentially greater role for anthracyclines in suppressing the aggressiveness of TOPO2A positive tumors (89).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

et al. 2017

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There has been an alarming rise in the incidence of esophageal adenocarcinoma which continues to have poor survival rates primarily due to lack of effective chemotherapy and presentation at advanced stages. Over a dozen chemotherapeutic agents are FDA approved for esophageal cancer (EC), and a two or three-drug combination is typically prescribed as first-line therapy for the majority of EC patients, administered either pre or post-operatively with esophageal resection. We have noticed significant variability in adjuvant and neoadjuvant regimens used in the community setting. The aim of this study was to review the various drug regimens used in the neoadjuvant setting for EC patients with adenocarcinoma undergoing resection at a single tertiary referral center in the Midwest. A total of 123 patients (stage II–III) underwent esophageal resection after neoadjuvant treatment at the center. Overall, 18 distinct drug regimens were used in 123 patients including two patients who received targeted therapy. Median survival post-surgery for this group was 11.2 months with no single regimen offering a survival advantage. These results reveal an unclear algorithm of how accepted regimens are prescribed in the community setting as well as a dire need for agents that are more effective. Additionally, it was noted that although proteomic markers have been found to predict drug response to 92% of the FDA-approved drugs in EC (12 of 13), according to pathology reports, molecular diagnostic testing was not used to direct treatment in this cohort. We therefore propose potential strategies to improve clinical outcomes including the use of a robust molecular oncology diagnostic panel and discuss the potential role for targeted chemotherapy and/or immunotherapy in the management of EC patients.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

et al. 2017

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“…Wittmann et al (23) confirmed that the high expression of TOP2A was associated with tumor metastasis and death outcome by analyzing 102 cases of nephroblastoma. A large-scale retrospective study has demonstrated that TOP2A high expression is associated with poor differentiation and neural invasion of esophageal cancer, and is also an independent risk factor affecting the prognosis of esophageal cancer (24). De Resende et al (25) have reported that high expression of TOP2A protein is associated with severe lymphatic vascular invasion and a low relapse-free survival rate in prostate cancer.…”

Section: Introductionmentioning

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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“…Considering the previously mentioned role of TopoIIα in cell division and its increased expression in the G2/M phase of the cell cycle, immunohistochemical staining for TopoIIα may be useful in the determination of cell proliferation, and eventually malignant transformation (9–11). Previous studies have considered TopoIIα as a prognostic factor in patients with esophageal squamous cell carcinomas, breast cancer, clear cell renal cell carcinoma and nasopharyngeal carcinoma (12–15). …”

Section: Introductionmentioning

confidence: 99%

DNA topoisomerase IIα and Ki67 are prognostic factors in patients with hepatocellular carcinoma

Cao

Shao-hu

et al. 2017

Oncology Letters

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The present study was designed to determine the significance of DNA topoisomerase IIa (TopoIIα) and Ki67 in hepatocellular carcinoma cells (HCCs). The present study included 353 patients with HCC. The association of clinicopathological data with the expression of TopoIIα and Ki67 by immunohistochemistry was analyzed by χ2 test. Cox multivariate proportional hazards regression analysis and Kaplan-Meier analysis were performed with all the variables to derive risk estimates associated with overall survival (OS)/recurrence-free survival (RFS) and to control for confounders. TopoIIα and Ki67 were detected in the nuclei of the tumor cells. With TopoIIα, 35.7% of cells exhibited high expression, which was associated with tumor-node-metastasis stage, tumor size and α-fetoprotein level. With Ki67, 37.1% of cells exhibited high expression, which was associated with tumor-node-metastasis stage, tumor size and α-fetoprotein level. Correlation was identified between the expression level of TopoIIα and Ki67 in HCCs (r=0.444). Multivariate analysis revealed that high TopoIIα expression is a prognostic indicator for RFS [hazard ratio (HR), 2.002; 95% confidence interval (CI), 1.429–2.806] and OS (HR, 2.749; 95% CI, 1.919–3.939), and high Ki67 expression is a prognostic indicator for OS (HR, 1.816; 95% CI, 1.273–2.589). The TopoIIα-low group had a significantly increased RFS rate (55.6 vs. 31.7%) and OS rate (66.5 vs. 23.8%) compared with the TopoIIα-high group. The OS rate was increased in the Ki67-low group compared with the Ki67-high group (67.0 vs. 26.5%). Expression of TopoIIα and Ki67 are independent prognostic factors for survival in HCCs. TopoIIα was positively associated with Ki67 expression.

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Topo2A as a prognostic biomarker for patients with resectable esophageal squamous cell carcinomas

Cited by 11 publications

References 33 publications

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

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

DNA topoisomerase IIα and Ki67 are prognostic factors in patients with hepatocellular carcinoma

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