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Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance

This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines a...

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Autores principales: Ricciardelli, Carmela, Lokman, Noor A., Pyragius, Carmen E., Ween, Miranda P., Macpherson, Anne M., Ruszkiewicz, Andrew, Hoffmann, Peter, Oehler, Martin K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392289/
https://www.ncbi.nlm.nih.gov/pubmed/28147318
http://dx.doi.org/10.18632/oncotarget.14867
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author Ricciardelli, Carmela
Lokman, Noor A.
Pyragius, Carmen E.
Ween, Miranda P.
Macpherson, Anne M.
Ruszkiewicz, Andrew
Hoffmann, Peter
Oehler, Martin K.
author_facet Ricciardelli, Carmela
Lokman, Noor A.
Pyragius, Carmen E.
Ween, Miranda P.
Macpherson, Anne M.
Ruszkiewicz, Andrew
Hoffmann, Peter
Oehler, Martin K.
author_sort Ricciardelli, Carmela
collection PubMed
description This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P < 0.0001) and overall survival (HR 1.28, P = 0.013) whilst high KRT6 mRNA was only associated with reduced progression-free survival (HR 1.2, P = 0.031). Both high K5/6 (≥ 10%, HR 1.78 95% CI; 1.03−2.65, P = 0.017) and high K5 (≥ 10%, HR 1.90, 95% CI; 1.12−3.19, P = 0.017) were associated with an increased risk of disease recurrence. KRT5 but not KRT6C mRNA expression was increased in chemotherapy resistant primary serous ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival.
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spelling pubmed-53922892017-04-21 Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance Ricciardelli, Carmela Lokman, Noor A. Pyragius, Carmen E. Ween, Miranda P. Macpherson, Anne M. Ruszkiewicz, Andrew Hoffmann, Peter Oehler, Martin K. Oncotarget Research Paper This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P < 0.0001) and overall survival (HR 1.28, P = 0.013) whilst high KRT6 mRNA was only associated with reduced progression-free survival (HR 1.2, P = 0.031). Both high K5/6 (≥ 10%, HR 1.78 95% CI; 1.03−2.65, P = 0.017) and high K5 (≥ 10%, HR 1.90, 95% CI; 1.12−3.19, P = 0.017) were associated with an increased risk of disease recurrence. KRT5 but not KRT6C mRNA expression was increased in chemotherapy resistant primary serous ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival. Impact Journals LLC 2017-01-27 /pmc/articles/PMC5392289/ /pubmed/28147318 http://dx.doi.org/10.18632/oncotarget.14867 Text en Copyright: © 2017 Ricciardelli et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ricciardelli, Carmela
Lokman, Noor A.
Pyragius, Carmen E.
Ween, Miranda P.
Macpherson, Anne M.
Ruszkiewicz, Andrew
Hoffmann, Peter
Oehler, Martin K.
Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance
title Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance
title_full Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance
title_fullStr Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance
title_full_unstemmed Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance
title_short Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance
title_sort keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392289/
https://www.ncbi.nlm.nih.gov/pubmed/28147318
http://dx.doi.org/10.18632/oncotarget.14867
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