Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma

Background: Cholangiocarcinoma (CCA) is a malignant tumor with an increasing incidence worldwide. Although radiation therapy has improved the therapeutic efficiency of CCA treatment, differential expression of genes among cholangiocarcinoma subtypes has been revealed through precise sequencing. Howe...

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Main Authors: Khaa Hoo Ong, Hong-Yue Lai, Ding-Ping Sun, Tzu-Ju Chen, Steven Kuan-Hua Huang, Yu-Feng Tian, Chia-Lin Chou, Yow-Ling Shiue, Ti-Chun Chan, Chien-Feng Li, Yu-Hsuan Kuo
Format: Article
Language:English
Published: IMR Press 2023-04-01
Series:Frontiers in Bioscience-Landmark
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Online Access:https://www.imrpress.com/journal/FBL/28/4/10.31083/j.fbl2804075
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author Khaa Hoo Ong
Hong-Yue Lai
Ding-Ping Sun
Tzu-Ju Chen
Steven Kuan-Hua Huang
Yu-Feng Tian
Chia-Lin Chou
Yow-Ling Shiue
Ti-Chun Chan
Chien-Feng Li
Yu-Hsuan Kuo
author_facet Khaa Hoo Ong
Hong-Yue Lai
Ding-Ping Sun
Tzu-Ju Chen
Steven Kuan-Hua Huang
Yu-Feng Tian
Chia-Lin Chou
Yow-Ling Shiue
Ti-Chun Chan
Chien-Feng Li
Yu-Hsuan Kuo
author_sort Khaa Hoo Ong
collection DOAJ
description Background: Cholangiocarcinoma (CCA) is a malignant tumor with an increasing incidence worldwide. Although radiation therapy has improved the therapeutic efficiency of CCA treatment, differential expression of genes among cholangiocarcinoma subtypes has been revealed through precise sequencing. However, no specific molecular therapeutic targets or biomarkers have been figured out for use in precision medicine, and the exact mechanism by which antitumorigenic effects occur is still unclear. Therefore, it is necessary to conduct further studies on the development and mechanisms associated with CCA. Methods: We examined the clinical data and pathological features of patients with cholangiocarcinomas. We investigated the associations between DNA Topoisomerase II Alpha (TOP2A) expression and patient outcomes, such as metastasis-free survival (MFS) and disease-specific survival (DSS), as well as clinical characteristics and pathological results. Results: TOP2A expression was shown to be upregulated in CCA tissue sections by immunohistochemistry staining and data mining. Moreover, we observed that the TOP2A expression correlated with clinical features, such as the primary tumor stage, histological variants, and patients with hepatitis. Furthermore, high expression of TOP2A was associated with worse survival outcomes in terms of the overall survival (p < 0.0001), disease-specific survival (p < 0.0001), and metastasis-free survival (p < 0.0001) compared with patients in the low TOP2A expression group. This indicates that a high level of TOP2A expression is related to an unfavorable prognosis. Conclusions: Our results show that TOP2A is highly expressed in CCA tissues, and its upregulation is correlated with the primary disease stage and poor prognosis significantly. Consequently, TOP2A is a prognostic biomarker and a novel therapeutic target for the treatment of CCA.
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spelling doaj.art-98b7e14fc15147e293eede3e99fbbc6f2023-04-28T09:24:06ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-04-012847510.31083/j.fbl2804075S2768-6701(23)00851-1Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in CholangiocarcinomaKhaa Hoo Ong0Hong-Yue Lai1Ding-Ping Sun2Tzu-Ju Chen3Steven Kuan-Hua Huang4Yu-Feng Tian5Chia-Lin Chou6Yow-Ling Shiue7Ti-Chun Chan8Chien-Feng Li9Yu-Hsuan Kuo10Division of Gastroenterology & General Surgery, Department of Surgery, Chi Mei Medical Center, 710 Tainan, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, 404333 Taichung, TaiwanDivision of Gastroenterology & General Surgery, Department of Surgery, Chi Mei Medical Center, 710 Tainan, TaiwanDepartment of Medical Technology, Chung Hwa University of Medical Technology, 717 Tainan, TaiwanDivision of Urology, Department of Surgery, Chi Mei Medical Center, 710 Tainan, TaiwanDivision of Colon and Rectal Surgery, Department of Surgery, Chi Mei Medical Center, 710 Tainan, TaiwanDepartment of Medical Technology, Chung Hwa University of Medical Technology, 717 Tainan, TaiwanInstitute of Biomedical Sciences, National Sun Yat-sen University, 804 Kaohsiung, TaiwanDepartment of Medical Research, Chi Mei Medical Center, 710 Tainan, TaiwanInstitute of Precision Medicine, National Sun Yat-sen University, 804 Kaohsiung, TaiwanInstitute of Biomedical Sciences, National Sun Yat-sen University, 804 Kaohsiung, TaiwanBackground: Cholangiocarcinoma (CCA) is a malignant tumor with an increasing incidence worldwide. Although radiation therapy has improved the therapeutic efficiency of CCA treatment, differential expression of genes among cholangiocarcinoma subtypes has been revealed through precise sequencing. However, no specific molecular therapeutic targets or biomarkers have been figured out for use in precision medicine, and the exact mechanism by which antitumorigenic effects occur is still unclear. Therefore, it is necessary to conduct further studies on the development and mechanisms associated with CCA. Methods: We examined the clinical data and pathological features of patients with cholangiocarcinomas. We investigated the associations between DNA Topoisomerase II Alpha (TOP2A) expression and patient outcomes, such as metastasis-free survival (MFS) and disease-specific survival (DSS), as well as clinical characteristics and pathological results. Results: TOP2A expression was shown to be upregulated in CCA tissue sections by immunohistochemistry staining and data mining. Moreover, we observed that the TOP2A expression correlated with clinical features, such as the primary tumor stage, histological variants, and patients with hepatitis. Furthermore, high expression of TOP2A was associated with worse survival outcomes in terms of the overall survival (p < 0.0001), disease-specific survival (p < 0.0001), and metastasis-free survival (p < 0.0001) compared with patients in the low TOP2A expression group. This indicates that a high level of TOP2A expression is related to an unfavorable prognosis. Conclusions: Our results show that TOP2A is highly expressed in CCA tissues, and its upregulation is correlated with the primary disease stage and poor prognosis significantly. Consequently, TOP2A is a prognostic biomarker and a novel therapeutic target for the treatment of CCA.https://www.imrpress.com/journal/FBL/28/4/10.31083/j.fbl2804075cholangiocarcinomadna topoisomerase (atp-hydrolyzing activity) activitytopoisomerase ii α (top2a)prognostic biomarker
spellingShingle Khaa Hoo Ong
Hong-Yue Lai
Ding-Ping Sun
Tzu-Ju Chen
Steven Kuan-Hua Huang
Yu-Feng Tian
Chia-Lin Chou
Yow-Ling Shiue
Ti-Chun Chan
Chien-Feng Li
Yu-Hsuan Kuo
Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma
Frontiers in Bioscience-Landmark
cholangiocarcinoma
dna topoisomerase (atp-hydrolyzing activity) activity
topoisomerase ii α (top2a)
prognostic biomarker
title Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma
title_full Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma
title_fullStr Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma
title_full_unstemmed Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma
title_short Prognostic Significance of DNA Topoisomerase II Alpha (TOP2A) in Cholangiocarcinoma
title_sort prognostic significance of dna topoisomerase ii alpha top2a in cholangiocarcinoma
topic cholangiocarcinoma
dna topoisomerase (atp-hydrolyzing activity) activity
topoisomerase ii α (top2a)
prognostic biomarker
url https://www.imrpress.com/journal/FBL/28/4/10.31083/j.fbl2804075
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