Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/105316
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Type: | Journal article |
Title: | Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance |
Author: | Ricciardelli, C. Lokman, N. Pyragius, C. Ween, M. Macpherson, A. Ruszkiewicz, A. Hoffmann, P. Oehler, M. |
Citation: | Oncotarget, 2017; 8(11):17819-17832 |
Publisher: | Impact Journals |
Issue Date: | 2017 |
ISSN: | 1949-2553 1949-2553 |
Statement of Responsibility: | Carmela Ricciardelli, Noor A Lokman, Carmen E Pyragius, Miranda P Ween, Anne M Macpherson, Andrew Ruszkiewicz, Peter Hoffmann, Martin K Oehler |
Abstract: | 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. |
Keywords: | Chemoresistance keratin 5 ovarian cancer recurrence tumor progression |
Rights: | All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. |
DOI: | 10.18632/oncotarget.14867 |
Published version: | http://dx.doi.org/10.18632/oncotarget.14867 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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File | Description | Size | Format | |
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hdl_105316.pdf | Published version | 11.09 MB | Adobe PDF | View/Open |
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