Overexpression of CD44 is associated with a poor prognosis in grade II/III gliomas

Hou, Chongxian; Ishi, Yukitomo; Motegi, Hiroaki; Okamoto, Michinari; Ou, Yafei; Chen, Jiawei; Yamaguchi, Shigeru

doi:10.1007/s11060-019-03288-8

Cited by 24 publications

(29 citation statements)

References 47 publications

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“…CD44s internalizes from cell surface to the endosomal compartments and inhibits Rab7A-mediated EGFR degradation [66] (Figure 2 and Table 2). Accordingly, CD44s expression correlates with highly invasive behavior and poor prognosis [67].…”

Section: Egfr Signaling Pathwaymentioning

confidence: 99%

Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Bielli

Pagliarini

Pieraccioli

et al. 2019

Cells

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Brain tumors are a heterogeneous group of neoplasms ranging from almost benign to highly aggressive phenotypes. The malignancy of these tumors mostly relies on gene expression reprogramming, which is frequently accompanied by the aberrant regulation of RNA processing mechanisms. In brain tumors, defects in alternative splicing result either from the dysregulation of expression and activity of splicing factors, or from mutations in the genes encoding splicing machinery components. Aberrant splicing regulation can generate dysfunctional proteins that lead to modification of fundamental physiological cellular processes, thus contributing to the development or progression of brain tumors. Herein, we summarize the current knowledge on splicing abnormalities in brain tumors and how these alterations contribute to the disease by sustaining proliferative signaling, escaping growth suppressors, or establishing a tumor microenvironment that fosters angiogenesis and intercellular communications. Lastly, we review recent efforts aimed at developing novel splicing-targeted cancer therapies, which employ oligonucleotide-based approaches or chemical modulators of alternative splicing that elicit an impact on brain tumor biology.

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Section: Egfr Signaling Pathwaymentioning

confidence: 99%

Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Bielli

Pagliarini

Pieraccioli

et al. 2019

Cells

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“…Previous studies indicated the potential prognostic value and clinicopathological signi cance of CD44 expression in glioma patients. However, the eligible studies included in this meta-analysis were diversi ed and the results were contradictory [52,53,[55][56][57][58][59][60][61][62][63][64][65][66]. The present meta-analysis systematically analyzed the prognostic impact of CD44s expression on glioma patients.…”

Section: Discussionmentioning

confidence: 99%

“…Fourteen studies [52,53,[55][56][57][58][59][60][61][62][63][64][65][66], including 743 patients, reported overall survival (OS) data using univariate analysis (Table 1). With substantial heterogeneity (P<0.0001, I 2 =72.2%), a pooled analysis in a random-effects model showed increased CD44s expression in glioma patients predicted reduced OS (pooled HR =1.63, 95% CI= [1.16, 2.29], P=0.005) ( Fig.…”

Section: Correlation Between Cd44s Expression and Overall Survivalmentioning

confidence: 99%

“…A total of 235 patients from four studies [60][61][62]67] were included in the univariate analysis of the correlation of CD44s expression with progression-free survival (PFS) ( Table 1…”

Section: Correlation Between Cd44s Expression and Progression-free Sumentioning

confidence: 99%

“…4). As shown in Table 4, no individual study could statistically signi cantly alter the combined results of survival outcomes and clinicopathological parameters, except the study by Hou CX et al [60] which can affect the pooled HR of CD44s expression on OS in multivariate analysis (Fig. 4B), the study by Du Q et al [79] included in the pooled analysis of the correlation between CD44v6 expression and WHO grades of glioma (Fig.…”

Section: Sensitivity Analysis and Publication Biasmentioning

confidence: 99%

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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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