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

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.

The prognostic value and clinicopathological significance of CD44 expression in ovarian cancer: a meta-analysis

“…In addition, although the mechanism remains unclear, CD44 and HA are both correlated with drug resistance [10]. Overall, CD44 is a potential prognostic marker for various diseases [48][49][50].…”

Identification of Biomarkers for Breast Cancer Using Databases

“…The oncogenic isoform of HER2, HER2Δ16, is expressed with HER2 in nearly 50% of HER2 positive breast tumors, and HER2Δ16 drives metastasis and resistance to drugs including tamoxifen and trastuzumab 32. Other molecules such as thyroid hormone receptor-interacting protein 13, DLDN11 , CD44, and midkine protein in breast cancer may be potential prognostic biomarkers and therapeutic targets 33–36…”

Up-modulation of PLC-β2 reduces the number and malignancy of triple-negative breast tumor cells with a CD133+/EpCAM+ phenotype: a promising target for preventing progression of TNBC

“…To better investigate the role of PLC-β2 in modulating the stem cell phenotype of TNBC cells, we also evaluated the surface expression of CD44, a well-described cancer stem cell marker in breast tumors and a negative prognosticator in TNBC [ 33 ]. The contemporary staining of MDA-MB-231 with anti-CD44, anti-CD133 and anti-EpCAM antibodies demonstrated that the over-expression of PLC-β2 reduces the number of CD44 + /CD133 + /EpCAM + cells.…”