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Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers

Epithelial ovarian cancers (EOCs) are highly lethal gynecological malignancies with a high recurrence rate. Therefore, developing prognostic markers for recurrence after chemotherapy is crucial for the treatment of ovarian cancers. As ovarian cancers frequently respond to DNA-damaging agents, we ass...

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Autores principales: Lee, Yoo-Kyung, Park, Noh-Hyun, Lee, Hyunsook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673471/
https://www.ncbi.nlm.nih.gov/pubmed/26584681
http://dx.doi.org/10.1038/emm.2015.85
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author Lee, Yoo-Kyung
Park, Noh-Hyun
Lee, Hyunsook
author_facet Lee, Yoo-Kyung
Park, Noh-Hyun
Lee, Hyunsook
author_sort Lee, Yoo-Kyung
collection PubMed
description Epithelial ovarian cancers (EOCs) are highly lethal gynecological malignancies with a high recurrence rate. Therefore, developing prognostic markers for recurrence after chemotherapy is crucial for the treatment of ovarian cancers. As ovarian cancers frequently respond to DNA-damaging agents, we assessed the clinicopathological significance of key double-strand DNA break (DSB) repair genes, including BRCA1, BRCA2, BARD1, ATM, RAD51 and NBS1 in EOC cell lines and paraffin-embedded tissue sections from 140 EOC patients treated with cytoreductive surgery, followed by platinum-based chemotherapy. These samples were analyzed for the clinicopathological impact of DSB genes by western blot analysis, immunohistochemistry and quantitative real-time PCR. Of the DSB repair genes, BRCA1, ATM and NBS1, which are involved in the homologous recombination-mediated repair pathway, were related to aggressive parameters in EOC. When survival analysis was performed, NBS1 expression exhibited an association with EOC recurrence. Specifically, increased NBS1 expression was found in 107 out of 140 cases (76.0%) and correlated with advanced stage (P=0.001), high grade (P=0.001) and serous histology (P=0.008). The median recurrence-free survival in patients with positive and negative expression of NBS1 was 30 and 78 months, respectively (P=0.0068). In multivariate analysis, NBS1 was an independent prognostic factor for the recurrence of EOC. Together, these results suggest that NBS1 is a marker of poor prognosis for the recurrence of EOC and is associated with aggressive clinicopathological parameters.
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spelling pubmed-46734712015-12-17 Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers Lee, Yoo-Kyung Park, Noh-Hyun Lee, Hyunsook Exp Mol Med Original Article Epithelial ovarian cancers (EOCs) are highly lethal gynecological malignancies with a high recurrence rate. Therefore, developing prognostic markers for recurrence after chemotherapy is crucial for the treatment of ovarian cancers. As ovarian cancers frequently respond to DNA-damaging agents, we assessed the clinicopathological significance of key double-strand DNA break (DSB) repair genes, including BRCA1, BRCA2, BARD1, ATM, RAD51 and NBS1 in EOC cell lines and paraffin-embedded tissue sections from 140 EOC patients treated with cytoreductive surgery, followed by platinum-based chemotherapy. These samples were analyzed for the clinicopathological impact of DSB genes by western blot analysis, immunohistochemistry and quantitative real-time PCR. Of the DSB repair genes, BRCA1, ATM and NBS1, which are involved in the homologous recombination-mediated repair pathway, were related to aggressive parameters in EOC. When survival analysis was performed, NBS1 expression exhibited an association with EOC recurrence. Specifically, increased NBS1 expression was found in 107 out of 140 cases (76.0%) and correlated with advanced stage (P=0.001), high grade (P=0.001) and serous histology (P=0.008). The median recurrence-free survival in patients with positive and negative expression of NBS1 was 30 and 78 months, respectively (P=0.0068). In multivariate analysis, NBS1 was an independent prognostic factor for the recurrence of EOC. Together, these results suggest that NBS1 is a marker of poor prognosis for the recurrence of EOC and is associated with aggressive clinicopathological parameters. Nature Publishing Group 2015-11 2015-11-20 /pmc/articles/PMC4673471/ /pubmed/26584681 http://dx.doi.org/10.1038/emm.2015.85 Text en Copyright © 2015 KSBMB. http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Article
Lee, Yoo-Kyung
Park, Noh-Hyun
Lee, Hyunsook
Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers
title Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers
title_full Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers
title_fullStr Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers
title_full_unstemmed Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers
title_short Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers
title_sort clinicopathological values of nbs1 and dna damage response genes in epithelial ovarian cancers
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673471/
https://www.ncbi.nlm.nih.gov/pubmed/26584681
http://dx.doi.org/10.1038/emm.2015.85
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