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Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer

BACKGROUD: As magicians of the DNA world, topoisomerases resolve all of the topological problems in relation to DNA during a variety of genetic processes. While the prognostic value of topoisomerase isoenzymes in epithelial ovarian carcinoma (EOC) is still elusive. In current study, we investigated...

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Autores principales: Bai, Yang, Li, Liang-Dong, Li, Jun, Lu, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912764/
https://www.ncbi.nlm.nih.gov/pubmed/27315793
http://dx.doi.org/10.1186/s13048-016-0244-9
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author Bai, Yang
Li, Liang-Dong
Li, Jun
Lu, Xin
author_facet Bai, Yang
Li, Liang-Dong
Li, Jun
Lu, Xin
author_sort Bai, Yang
collection PubMed
description BACKGROUD: As magicians of the DNA world, topoisomerases resolve all of the topological problems in relation to DNA during a variety of genetic processes. While the prognostic value of topoisomerase isoenzymes in epithelial ovarian carcinoma (EOC) is still elusive. In current study, we investigated the prognostic value of topoisomerase isoenzymes in the EOC patients. Kaplan Meier plotter (KM plotter) database were used to assess the relevance of individual topoisomerase isoenzyme mRNA expression to EOC patients overall survival (OS), in which updated survival information and gene expression data were from a total of 1,648 EOC patients. RESULTS: High expression of TOP1 and TOP2A were found to be correlated to worse OS in all patients and serous patients, but not in endometrioid patients. Contrary to TOP1 and TOP2A, TOP3A and TOP3B expression were associated with better OS in all patients and serous patients, but not in endometrioid patients. While TOP2B were not found any significant prognostic value for EOC patients. From the Oncomine database, we also found widespread upregulation in the expression of TOP1 and TOP2A genes in primary tumor tissues. Albeit limited in number, all datasets exhibiting differential expression showed TOP3A and TOP3B under-regulated. CONCLUSION: These results strongly supported that TOP1 and TOP2A were potential biomarkers for predicting poor survival of EOC patients, while TOP3A and TOP3B were expected to be further exploited as tumor suppressors. Comprehensive understanding of the topoisomerase isoforms may have guiding significance for the diagnosis treatment and prognosis in EOC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-016-0244-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-49127642016-06-19 Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer Bai, Yang Li, Liang-Dong Li, Jun Lu, Xin J Ovarian Res Research BACKGROUD: As magicians of the DNA world, topoisomerases resolve all of the topological problems in relation to DNA during a variety of genetic processes. While the prognostic value of topoisomerase isoenzymes in epithelial ovarian carcinoma (EOC) is still elusive. In current study, we investigated the prognostic value of topoisomerase isoenzymes in the EOC patients. Kaplan Meier plotter (KM plotter) database were used to assess the relevance of individual topoisomerase isoenzyme mRNA expression to EOC patients overall survival (OS), in which updated survival information and gene expression data were from a total of 1,648 EOC patients. RESULTS: High expression of TOP1 and TOP2A were found to be correlated to worse OS in all patients and serous patients, but not in endometrioid patients. Contrary to TOP1 and TOP2A, TOP3A and TOP3B expression were associated with better OS in all patients and serous patients, but not in endometrioid patients. While TOP2B were not found any significant prognostic value for EOC patients. From the Oncomine database, we also found widespread upregulation in the expression of TOP1 and TOP2A genes in primary tumor tissues. Albeit limited in number, all datasets exhibiting differential expression showed TOP3A and TOP3B under-regulated. CONCLUSION: These results strongly supported that TOP1 and TOP2A were potential biomarkers for predicting poor survival of EOC patients, while TOP3A and TOP3B were expected to be further exploited as tumor suppressors. Comprehensive understanding of the topoisomerase isoforms may have guiding significance for the diagnosis treatment and prognosis in EOC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-016-0244-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-06-18 /pmc/articles/PMC4912764/ /pubmed/27315793 http://dx.doi.org/10.1186/s13048-016-0244-9 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bai, Yang
Li, Liang-Dong
Li, Jun
Lu, Xin
Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer
title Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer
title_full Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer
title_fullStr Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer
title_full_unstemmed Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer
title_short Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer
title_sort targeting of topoisomerases for prognosis and drug resistance in ovarian cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912764/
https://www.ncbi.nlm.nih.gov/pubmed/27315793
http://dx.doi.org/10.1186/s13048-016-0244-9
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