TY - JOUR
T1 - The prognostic effect of DDX3 upregulation in distant breast cancer metastases
AU - Dutch Distant Breast Cancer Metastases Consortium
AU - Heerma van Voss, Marise R.
AU - Schrijver, Willemijne A.M.E.
AU - ter Hoeve, Natalie D.
AU - Hoefnagel, Laurien D.
AU - Manson, Quirine F.
AU - van der Wall, Elsken
AU - Raman, Venu
AU - van Diest, Paul J.
N1 - Funding Information:
This work was financially supported by Utrecht University Alexandre Suerman Stipend (MHVV), the Dutch Cancer Foundation (UU2013-5851; MHVV), Flight Attendant Medical Research Institute (VR) and Safeway (VR).
Publisher Copyright:
© 2016, The Author(s).
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Brain metastasis
KW - Breast cancer
KW - DDX3
KW - DDX3X
KW - DEAD box RNA helicases
KW - Metastasis
UR - http://www.scopus.com/inward/record.url?scp=85006741571&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006741571&partnerID=8YFLogxK
U2 - 10.1007/s10585-016-9832-8
DO - 10.1007/s10585-016-9832-8
M3 - Article
C2 - 27999982
AN - SCOPUS:85006741571
SN - 0262-0898
VL - 34
SP - 85
EP - 92
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 1
ER -