Prognostic Significance of CD24 and CD44 in Breast Cancer: A Meta-Analysis

Wang, Zhu; Wang, Qianqian; Wang, Qi; Wang, Yanping; Chen, Jie

doi:10.5301/jbm.5000224

Cited by 51 publications

(45 citation statements)

References 36 publications

(53 reference statements)

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“…To date, only the particular variant CD44v6 was found to be related to aggressive tumor behavior and prognosis in breast cancer. 31 , 35 This meta-analysis revealed that CD44v6 expression was associated with histological grade, lymph node metastasis, and poor prognosis in breast cancer. CD44v6 also has great implications for targeted therapy and prognostic imaging.…”

Section: Discussionmentioning

confidence: 96%

Prognostic value of CD44v6 expression in breast cancer: a meta-analysis

Qiao

Song

Deng

et al. 2018

OTT

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PurposeThe prognostic value and clinical significance of CD44 variant isoform v6 (CD44v6) in breast cancer remains controversial. Our study aimed to generalize the correlation between CD44v6 expression and clinicopathological features and prognosis in breast cancer by using a meta-analysis.MethodsWe performed a comprehensive search of relevant literature from PubMed, Cochrane Database, and EMBASE database that were published before January 2018. The pooled ORs and HRs with 95% CIs were used to estimate the effects.ResultsThirteen articles comprising 1,458 patients were included for analysis. The results revealed that CD44v6 expression was associated with histological grade (overall: OR=1.56, 95% CI [1.06, 2.29], P=0.023; Asian: OR=1.78, 95% CI [1.12, 2.85], P=0.016) and lymph node metastasis (overall: OR=1.96, 95% CI [1.01, 3.78], P=0.046; Asian: OR=2.11, 95% CI [1.00, 4.44], P=0.049). CD44v6 expression was significantly associated with poor prognosis in patients with breast cancer (overall survival: overall: HR=1.55, 95% CI [1.09, 2.22], P=0.015; Asian: HR=2.22, 95% CI [1.34, 3.68], P=0.002).ConclusionOur meta-analysis demonstrates that CD44v6 is significantly associated with poor prognosis, histological grade, and lymph node metastasis in breast cancer patients, especially among Asian patients.

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Section: Discussionmentioning

confidence: 96%

Prognostic value of CD44v6 expression in breast cancer: a meta-analysis

Qiao

Song

Deng

et al. 2018

OTT

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“…However, CD24 expression can also confer adhesive properties enabling invasion. In a meta-analysis of 16 studies of 5,697 breast cancers, CD24 was found to be signi cantly associated with poorer survival [90], presumably due to non EMP functions. In studies on breast cancer cell lines in vivo, CD24 was found to act as a ligand for P-selectin on the lung vascular endothelium [64].…”

Section: Discussionmentioning

confidence: 99%

Integrins Alpha-2 and Beta-1 expression increases through Multiple Generations of the EDW01 Patient-Derived Xenograft Model of Breast Cancer - insight into their role in Epithelial Mesenchymal Transition in vivo gained from an in vitro model system

Wafai

Williams

Souza

et al. 2020

Preprint

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Background: Breast cancers acquire aggressive capabilities via epithelial to mesenchymal transition (EMT), in which various integrins/integrin linked kinase signalling are upregulated. Methods: We investigated this in two patient-derived xenografts (PDXs) developed from breast-to-bone metastases, and it’s functional significance in a breast cancer cell line system. ED03 and EDW01 PDXs were grown subcutaneously in immunocompromised SCID mice through 11 passages and 7 passages, respectively. Tumour tissue was assessed using immunohistochemistry (IHC) for estrogen receptor (ER)-alpha, E-cadherin, vimentin, Twist1, beta-catenin, P120-RasGAP, CD44, CD24 and Ki67, and RT-qPCR of EMT-related factors (CDH1, VIM, CD44, CD24), integrins beta 1 (ITGB1), alpha 2 (ITGA2) and ILK. Integrin and ILK expression in epidermal growth factor (EGF) induced EMT of the PMC42-ET breast cancer cell line was assessed by RT-qPCR and Western blotting, as were the effects of their transient knockdown via small interfering RNA +/- EGF. Cell migration, changes in cell morphology and adhesion of siRNA-transfected PMC42-ET cells to various extracellular matrix (ECM) substrates was assessed.Results: The ED03 (ER+/PR-/HER2-/lobular) and EDW01 (ER+/PR-/HER2-/ductal) PDXs were both classified as molecular subtype luminal A. ED03 xenografts exhibited mutated E-cadherin with minimal expression, but remained vimentin-negative across all passages. In EDW01, the hypoxic indicator gene CAIX and Twist1 were co-ordinately upregulated at passage 4-5, corresponding with a decrease in E-cadherin. At passages 6-7, VIM was upregulated along with ITGB1 and ITGA2, consistent with an increasing EMT. The ED03 PDX displayed minimal change over passages in mice, for all genes examined. ILK, ITGB1 and ITGA2 mRNAs were also increased in the EGF-induced EMT of PMC42-ET cells (in which CDH1 was downregulated) although siRNA against these targets revealed that this induction was not necessary for the observed EMT. However, their knockdown significantly reduced EMT-associated adhesion and Transwell migration.Conclusion: Our data suggest that despite an increase in ITGA2 and ITGB1 gene expression in the EMT exhibited by EDW01 PDX over multiple generations, this pathway may not necessarily drive the EMT process.

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“…In recent years, CD24 overexpression has been correlated with shorter patient survival in breast cancer, ovarian cancer, non-small cell lung carcinomas, prostate tumors, colorectal cancer, and in esophageal squamous cell carcinoma (Kristiansen et al, 2002, 2003, 2004a; Choi et al, 2005; Sano et al, 2009; Majores et al, 2015; Wang et al, 2016). CD24 expression has also been associated with bladder tumor recurrence (Liu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

CD24 Expression Is Increased in 5-Fluorouracil-Treated Esophageal Adenocarcinoma Cells

et al. 2017

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The cancer stem cell (CSC) model suggests that there are subsets of cells within a tumor with increased proliferation and self-renewal capacity, which play a key role in therapeutic resistance. The importance of cyclooxygenase-2 (COX-2) in carcinogenesis has been previously established and the use of COX-2 inhibitors as celecoxib has been shown to exert antitumor effects. The present study investigated whether treatment of esophageal adenocarcinoma (EAC) cells with 5-fluorouracil (5-FU) or the growth of tumor spheres increased the proportion of CSCs and also if treatment with celecoxib was able to reduce the putative CSC markers in this tumor. OE19 and OE33 EAC cells surviving 5-FU exposure exhibited an increase in CSC markers CD24 and ABCG2 and also an increased resistance to apoptosis. EAC cell lines had the capacity to form multiple spheres displaying typical CSC functionalities such as self-renewal and increased CD24 levels. In addition, after the induction of differentiation, cancer cells reached levels of CD24 similar to those observed in the parental cells. Treatment with celecoxib alone or in combination with 5-FU also resulted in a reduction of CD24 expression. Moreover, celecoxib inhibited the growth of tumor spheres. These findings showing a reduction in CSC markers induced by celecoxib suggest that the COX-2 inhibitor might be a candidate for combined chemotherapy in the treatment of EAC. However, additional clinical and experimental studies are needed.

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Prognostic Significance of CD24 and CD44 in Breast Cancer: A Meta-Analysis

Cited by 51 publications

References 36 publications

Prognostic value of CD44v6 expression in breast cancer: a meta-analysis

Prognostic value of CD44v6 expression in breast cancer: a meta-analysis

Integrins Alpha-2 and Beta-1 expression increases through Multiple Generations of the EDW01 Patient-Derived Xenograft Model of Breast Cancer - insight into their role in Epithelial Mesenchymal Transition in vivo gained from an in vitro model system

CD24 Expression Is Increased in 5-Fluorouracil-Treated Esophageal Adenocarcinoma Cells

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