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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 1/2017

Open Access 01-01-2017 | Research Paper

The prognostic effect of DDX3 upregulation in distant breast cancer metastases

Authors: Marise R. Heerma van Voss, Willemijne A. M. E. Schrijver, Natalie D. ter Hoeve, Laurien D. Hoefnagel, Quirine F. Manson, Elsken van der Wall, Venu Raman, Paul J. van Diest, Dutch Distant Breast Cancer Metastases Consortium

Published in: Clinical & Experimental Metastasis | Issue 1/2017

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Abstract

Metastatic breast cancer remains one of the leading causes of death in women and identification of novel treatment targets is therefore warranted. Functional studies showed that the RNA helicase DDX3 promotes metastasis, but DDX3 expression was never studied in patient samples of metastatic cancer. In order to validate previous functional studies and to evaluate DDX3 as a potential therapeutic target, we investigated DDX3 expression in paired samples of primary and metastatic breast cancer. Samples from 79 breast cancer patients with distant metastases at various anatomical sites were immunohistochemically stained for DDX3. Both cytoplasmic and nuclear DDX3 expression were compared between primary and metastatic tumors. In addition, the correlation between DDX3 expression and overall survival was assessed. Upregulation of cytoplasmic (28%; OR 3.7; p = 0.002) was common in breast cancer metastases, especially in triple negative (TN) and high grade cases. High cytoplasmic DDX3 levels were most frequent in brain lesions (65%) and significantly correlated with high mitotic activity and triple negative subtype. In addition, worse overall survival was observed for patients with high DDX3 expression in the metastasis (HR 1.79, p = 0.039). Overall, we conclude that DDX3 expression is upregulated in distant breast cancer metastases, especially in the brain and in TN cases. In addition, high metastatic DDX3 expression correlates with worse survival, implying that DDX3 is a potential therapeutic target in metastatic breast cancer, in particular in the clinically important group of TN patients.
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Metadata
Title
The prognostic effect of DDX3 upregulation in distant breast cancer metastases
Authors
Marise R. Heerma van Voss
Willemijne A. M. E. Schrijver
Natalie D. ter Hoeve
Laurien D. Hoefnagel
Quirine F. Manson
Elsken van der Wall
Venu Raman
Paul J. van Diest
Dutch Distant Breast Cancer Metastases Consortium
Publication date
01-01-2017
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 1/2017
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-016-9832-8

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