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

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dc.contributor.authorRicciardelli, C.
dc.contributor.authorLokman, N.
dc.contributor.authorPyragius, C.
dc.contributor.authorWeen, M.
dc.contributor.authorMacpherson, A.
dc.contributor.authorRuszkiewicz, A.
dc.contributor.authorHoffmann, P.
dc.contributor.authorOehler, M.
dc.date.issued2017
dc.description.abstractThis 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.
dc.description.statementofresponsibilityCarmela Ricciardelli, Noor A Lokman, Carmen E Pyragius, Miranda P Ween, Anne M Macpherson, Andrew Ruszkiewicz, Peter Hoffmann, Martin K Oehler
dc.identifier.citationOncotarget, 2017; 8(11):17819-17832
dc.identifier.doi10.18632/oncotarget.14867
dc.identifier.issn1949-2553
dc.identifier.issn1949-2553
dc.identifier.orcidRicciardelli, C. [0000-0001-7415-1854]
dc.identifier.orcidLokman, N. [0000-0002-2071-5308]
dc.identifier.orcidWeen, M. [0000-0002-0600-4585]
dc.identifier.orcidMacpherson, A. [0000-0002-7674-9961]
dc.identifier.orcidRuszkiewicz, A. [0000-0001-9052-4948]
dc.identifier.orcidOehler, M. [0000-0002-2651-5913]
dc.identifier.urihttp://hdl.handle.net/2440/105316
dc.language.isoen
dc.publisherImpact Journals
dc.rightsAll site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
dc.source.urihttps://doi.org/10.18632/oncotarget.14867
dc.subjectChemoresistance
dc.subjectkeratin 5
dc.subjectovarian cancer
dc.subjectrecurrence
dc.subjecttumor progression
dc.titleKeratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance
dc.typeJournal article
pubs.publication-statusPublished

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