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Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis

Authors Xu H, Tian Y, Yuan X, Liu Y, Wu H, Liu Q, Wu GS, Wu K

Received 26 September 2015

Accepted for publication 27 November 2015

Published 21 January 2016 Volume 2016:9 Pages 431—444

DOI https://doi.org/10.2147/OTT.S97192

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 2

Editor who approved publication: Professor Daniele Santini


Hanxiao Xu,1 Yijun Tian,1 Xun Yuan,1 Yu Liu,2 Hua Wu,1 Qian Liu,1 Gen Sheng Wu,3,4 Kongming Wu1

1Department of Oncology, 2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Oncology, 4Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA


Abstract: Cluster of differentiation 44 (CD44) is a transmembrane glycoprotein that serves as the receptor for the extracellular matrix component hyaluronic acid. CD44 has been reported to play key roles in cell proliferation, motility, and survival, but its role in breast cancer remains controversial. In this study, we conducted a meta-analysis. A total of 23 published Gene Expression Omnibus databases were included to evaluate the association between CD44 mRNA expression and clinicopathological characteristics or prognosis of the patients with breast cancer. Our analysis revealed that CD44 expression was associated with clinicopathological features, including the histological grade, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor-2 status. Higher levels of CD44 expression were observed in the basal subtype of breast cancer both at the mRNA and protein levels (odds ratio [OR] =2.08, 95% confidence interval [CI]: 1.72–2.52; OR =2.11, 95% CI: 1.67–2.68). Patients with CD44 overexpression exhibited significantly worse overall survival (hazard ratio =1.27; 95% CI: 1.04–1.55). Whole gene profile analysis revealed that CD44 expression was enriched in basal-type breast cancer and correlated with epithelial–mesenchymal transition and cancer stem cell gene profiles. In summary, our analyses indicated that CD44 potentially might be a prognostic marker for breast cancer and thus can serve as a therapeutic target for basal-type breast cancer.

Keywords: breast cancer, CD44, survival prediction, meta-analysis, biomarker

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