Prognostic role of the cancer stem cell marker CD44 in ovarian cancer: a meta-analysis

Shi, Yangyang; Jiang, Hui

doi:10.4238/gmr.15038325

Cited by 7 publications

(5 citation statements)

References 23 publications

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“…Stem cell markers have the main function of controlling the embryonal stem cells self-renewal and differentiation and maintaining the biological characteristics [23]. CD44 is a hyaluronic acid receptor and has been found to participate in diverse cellular processes, such as tumor metastasis, cell migration, proliferation [24]. Its elevation has been shown to be correlated to poor prognosis of numerous cancer types [25].…”

Section: Discussionmentioning

confidence: 99%

Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway

et al. 2019

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Background Ovarian cancer is known as one of the most common cancers in the world among women. ST6GALNAC1 is highly expressed in cancer stem cells (CSCs), which correlates to high tumor-initiating, self-renewal and differentiation abilities. This present study aims to investigate how ST6GALNAC1 affects ovarian cancer stem cells (OCSCs). Methods In order to identify the differentially expressed genes related to ovarian cancer, microarray-based gene expression profiling of ovarian cancer was used, and ST6GALANC1 was one of the identified targets. After that, levels of ST6GALNAC1 in OCSCs and ovarian cancer cells were examined. Subsequently, an Akt signaling pathway inhibitor LY294002 was introduced into the cluster of differentiation 90 + (CD90 + ) stem cells, and cell proliferation, migration and invasion, levels of CXCL16, EGFR, CD44, Nanog and Oct4, as well as tumorigenicity of OCSCs were examined. Results By using a comprehensive microarray analysis, it was determined that ST6GALNAC1 was highly expressed in ovarian cancer and it regulated the Akt signaling pathway. High levels of ST6GALNAC1 were observed in OCSCs and ovarian cancer cells. Silencing ST6GALNAC1 was shown to be able to reduce cell proliferation, migration, invasion, self-renewal ability, tumorigenicity of OCSCs. In accordance with these results, the effects of ST6GALNAC1 in OCSCs were dependent on the Akt signaling pathway. Conclusions When taken together, our findings defined the potential stimulative roles of ST6GALNAC1 in ovarian cancer and OCSCs, which relied on the Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway

et al. 2019

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“…An ovarian cancer tissue microarray analysis of paired primary, metastatic and recurrent tumor tissues from 26 patients, demonstrated that the metastatic as well as recurrent ovarian cancer tissues expressed higher levels of CD44 than the primary tumor (14). In addition, a meta-analysis unveiled that patients with CD44 was associated with poor prognosis in ovarian cancer patients, and that a CD44 + status was associated with common clinicopathological features and poor prognostic factors (5).…”

Section: Discussionmentioning

confidence: 99%

Effects of CD44 and E‑cadherin overexpression on the proliferation, adhesion and invasion of ovarian cancer cells

et al. 2017

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Abstract. CD44 is a prognostic indicator of shorter survival time in ovarian cancer. E-cadherin fragmentation promotes the progression of ovarian cancer. However, the effects of CD44 and E-cadherin overexpression on ovarian cancer cells have remained elusive. The present study aimed to investigate the effects of overexpression of CD44 and E-cadherin on cell proliferation, adhesion and invasion of SKOV-3 and OVCAR-3 ovarian cancer cells. Overexpression of CD44 and E-cadherin was achieved by transfecting SKOV-3 and OVCAR-3 cells with viruses carrying the CD44 or E-cadherin gene, respectively. Expression of CD44 and E-cadherin was detected by western blot analysis. The proliferation of SKOV-3 and OVCAR-3 cells was measured by a Cell Counting Kit-8 at 0, 24 and 48 h after viral transfection. The adhesion ability of SKOV-3 and OVCAR-3 cells to the endothelial layer was detected. A Transwell invasion assay was utilized to assess the invasion ability of the cells. Overexpression of CD44 and E-cadherin in SKOV-3 and OVCAR-3 cells was confirmed by western blot. Compared with the blank or negative control groups, the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells exhibited an increased cell proliferation rate at 24 and 48 h, whereas overexpression of E-cadherin did not alter the proliferation of these cells. Furthermore, compared with the blank and negative control groups, the cell adhesion and invasion ability in the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells was markedly higher. There were no significant differences in adhesion ability between the E-cadherin overexpression group and the blank/negative control group. Of note, overexpression of E-cadherin decreased the invasive ability of SKOV-3 and OVCAR-3 cells. In conclusion, Overexpression of CD44 increased the proliferation, adhesion and invasion of ovarian cancer cells, while overexpression of E-cadherin decreased the invasion of ovarian cancer cells. IntroductionOvarian cancer is a common malignant tumor type of the female reproductive system with a high mortality rate. The 5-year survival rate of patients with ovarian cancer is 25-30% (1). Although progress has been made in the treatment of ovarian cancer, the mortality rate remains high. The majority of ovarian cancer patients have tumor metastasis at the time-point of diagnosis, and tumor invasion and metastasis are important causes of treatment failure (2). Therefore, investigation of the molecular mechanisms involved in tumor proliferation, adhesion and invasion is of great importance for improving the therapeutic effectiveness of ovarian cancer treatments.CD44 is a transmembrane protein that mediates cell-cell interactions as well as cell adhesion and migration. It is widely expressed on the cell surface (3). CD44 participates in numerous biological processes such as tumor metastasis, hematopoiesis, lymphocyte activation, recirculation and homing. CD44 is a receptor for hyaluronic acid and interacts with other ligands, such as matrix metalloproteinases, collagens and osteopontin (3). Posit...

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“…The prognostic value of CD44 for patients with cancer has been widely validated in various solid tumors, such as hepatocellular carcinoma [37,38], non-small cell lung cancer [39][40][41], gastric cancer [42][43][44][45], ovarian cancer [46][47][48], colorectal cancer [49,50], etc. Some studies have demonstrated that the overexpression of CD44s is a poor prognostic factor for gliomas [51].…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological and Prognostic Significance of CD44s and CD44v6 Expression in Patients with Glioma: A Systematic Review and Meta-analysis

Xie¹,

Zhang²,

Xing³

et al. 2020

Preprint

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Background: Cancer stem cell surface marker CD44 has been revealed to promote tumor growth, progression, and metastasis in gliomas. Although the prognostic and clinicopathological value of CD44 standard form (CD44s) and its variant isoform CD44v6 expression in glioma patients has been evaluated in several independent studies, their results remained controversial. Therefore, we performed this meta-analysis to investigate the prognostic and clinicopathological association of CD44s/CD44v6 expression with glioma patients.Methods: A comprehensive literature search was performed in the electronic databases PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wangfang Data. The statistical analysis was conducted using Stata 15.0 and Review Manager 5.3.Results: A total of 43 studies with 2817 glioma patients were included in this meta-analysis. Pooled results indicated that positive expression of CD44s was significantly associated with poorer overall survival (OS, univariate analysis, HR =1.63, 95% CI= [1.16–2.29], P=0.005; multivariate analysis, HR=2.14, 95%CI= [1.21, 3.78], P=0.009), and reduced progression-free survival (PFS) in the univariate analysis (HR=2.09, 95% CI= [1.59, 2.75], P<0.00001), but not with PFS in the multivariate analysis (P>0.05) or tumor recurrence (P>0.05). CD44 expression was significantly upregulated in glioma tissues when compared with non-tumorous brain tissues (CD44s, OR=31.31, 95% CI= [15.22, 64.43], P<0.00001; CD44v6, OR=13.18, 95% CI= [5.51, 31.51], P<0.00001). In particular, CD44 expression was preferentially expressed in high-grade gliomas (grade III-IV vs. grade I-II, CD44s, OR=4.67, 95% CI= [3.18, 6.87], P<0.00001; CD44v6, OR=2.06, 95% CI= [1.21, 3.51], P=0.008). CD44s expression was lower in brain metastases than that in primary gliomas (OR=0.25, 95% CI= [0.10, 0.60], P=0.002), however, higher expression of CD44v6 was detected in brain metastases when compared with primary gliomas (OR=49.44, 95% CI= [13.06, 187.22], P<0.00001).Conclusions:This meta-analysis revealed the prognostic value of CD44s expression and clinicopathological significance of CD44s/CD44v6 expression in gliomas. Increased CD44s expression can predict worse prognosis of glioma patients. Particularly, CD44s is an independent prognostic factor for poor OS of glioma patients. Both CD44s and CD44v6 were glioma patients predominantly expressed in glioma tissues, especially in high-grade gliomas. Additionally, CD44v6 is a potential diagnostic biomarker for differentiating brain metastases from primary gliomas in individual cases. Therapeutic strategies targeting CD44 in gliomas should be further explored in the future.

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Prognostic role of the cancer stem cell marker CD44 in ovarian cancer: a meta-analysis

Cited by 7 publications

References 23 publications

Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway

Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway

Effects of CD44 and E‑cadherin overexpression on the proliferation, adhesion and invasion of ovarian cancer cells

Clinicopathological and Prognostic Significance of CD44s and CD44v6 Expression in Patients with Glioma: A Systematic Review and Meta-analysis

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