Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival: validatory study of two independent patient cohorts

Andersson, Gustav; Wennersten, Christoffer; Gaber, Alexander; Boman, Karolina; Nodin, Björn; Uhlén, Mathias; Segersten, Ulrika; Malmström, Per‐Uno; Jirström, Karin

doi:10.1186/1471-2490-14-36

Cited by 22 publications

(24 citation statements)

References 24 publications

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“…Non‐expression of ezrin has been more commonly observed in colorectal adenocarcinoma with poor prognostic factors, leading to late‐stage tumours and short survival times . Negative or weak ezrin expression in serous ovarian and urothelial bladder has also been reported, and correlated with poor patient outcome . Similarly, we have shown that, in CCAs, non‐expression or low expression of ezrin is more frequently observed in peripheral CCA than in perihilar CCA.…”

Section: Discussionsupporting

confidence: 67%

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Loss of ezrin in human intrahepatic cholangiocarcinoma is associated with ectopic expression of E‐cadherin

et al. 2016

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Section: Discussionsupporting

confidence: 67%

“…These data suggest a potential role of ezrin in cholangiocarcinogenesis. Indeed, ezrin expression has been analysed in several other human malignancies, and has been related to cancer progression and poor outcome …”

Section: Introductionmentioning

confidence: 99%

Loss of ezrin in human intrahepatic cholangiocarcinoma is associated with ectopic expression of E‐cadherin

et al. 2016

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“…This conclusion is further strengthened by recent multiple observations that miR-144 is consistently downregulated in many different types of cancers [20][21][22]. The cytosolic protein Ezrin is a member of ERM (Ezrin, radixin, moesin) protein family which plays important roles in regulation of cell adhesion and in the linkage between membrane proteins and contributes to tumor progression and development promoting cell survival, migration, and invasion [23,24]. Ezrin is overexpressed in aggressive tumors, and its activity is controlled by several signaling pathways involved in metastasis.…”

Section: Introductionmentioning

confidence: 49%

MicroRNA-144 inhibits the proliferation, apoptosis, invasion, and migration of osteosarcoma cell line F5M2

Cui

Wang

2015

Tumor Biol.

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This study is aimed to investigate the role of microRNA-144 (miR-144) in osteosarcoma cell line F5M2 proliferation, apoptosis, invasion, and metastasis. Between 2007 and 2014, 66 cases of osteosarcoma samples in the corresponding adjacent normal tissue samples were selected from surgical resection or biopsy in the Department of Orthopedics, Shengjing Hospital, China Medical University. MiR-144 levels and Ezrin messenger RNA (mRNA) levels in osteosarcoma and the adjacent bone tissues were detected, and clinical and pathological features were analyzed. Exogenous miR-144 was transfected into human osteosarcoma cell lines at two different concentrations (low and high), and the expression levels of miR-144 and Ezrin protein between highly metastatic osteosarcoma cells and lowly metastatic osteosarcoma cells were compared. Real-time polymerase chain reaction (RT-PCR) and Western blot were used for detecting the expression levels of miR-144 or Ezrin protein, respectively. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. Cell invasion and migration was evaluated by Transwell assays. Finally, flow cytometry was employed to determine the cell apoptosis. MiR-144 expression in osteosarcoma tissue was significantly lower than that in the surrounding normal bone tissue (P < 0.001), while Ezrin mRNA expression in osteosarcoma tissue was significantly higher than that in the surrounding normal bone tissue (P < 0.001); correlation analysis showed a significant negative correlation between miR-144 and Ezrin mRNA levels (r = 0.982, P < 0.001). MiR-144 and Ezrin mRNA expressions were significantly related with cell metastasis (P < 0.05) but were not related with other clinical factors such as gender, age, tumor location, tumor size, Enneking staging, and Dahlin's histological classification. The results of RT-PCR showed that the expression level of miR-144 in osteosarcoma cells increased after transfected with exogenous miR-144 mimics, and this increase positively correlated with the transfection concentration of miR-144 mimics. Furthermore, Western blotting revealed a significant and dose-dependent decrease in Ezrin protein levels in F5M2 cells transfected with miR-144. MTT and Transwell assays showed that the invasion and metastasis of F5M2 cells was significantly decreased following exogenous overexpression of miR-144. Our study supports the view that the miR-144 may regulate Ezrin protein expression by inhibiting the invasion and metastasis of osteosarcoma cells.

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“…Due to the potential importance of ezrin in cancer, the prognostic significance of ezrin has been evaluated in numerous types of cancers [13][14][15][16]. However, the results have been somewhat contradictory [15,17,18]. Recent meta-analyses have revealed that elevated ezrin expression is associated with poor prognosis in patients with a variety of solid tumors [19,20].…”

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confidence: 99%

The clinical prognostic significance of ezrin in patients with bone and soft tissue sarcomas: a meta‐analysis

Wang

et al. 2019

FEBS Open Bio

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Ezrin is a member of the ezrin–radixin–moesin (ERM) protein family and has been shown to be associated with poor prognosis in patients with a variety of solid tumors. However, the clinical prognostic significance of ezrin in patients with bone and soft tissue sarcomas remains unclear. Here, we performed a systematic meta‐analysis by searching PubMed, the Cochrane Library Database, EMBASE, the Web of Science, and the CBM, WanFang Med Online and CNKI databases. In total, 19 studies with a total of 1316 bone and soft tissue sarcoma patients were included. Pooled analyses showed that ezrin overexpression was correlated with a higher rate of tumor metastasis (OR 6.59, 95% CI: 2.84–15.33, P < 0.01, PFDR < 0.01) and recurrence (OR 3.18, 95% CI: 1.88–5.37, P < 0.01, PFDR < 0.01) and a more advanced tumor grade (OR 3.252, 95% CI: 1.371–7.715, P = 0.01, PFDR = 0.03). Moreover, elevated ezrin expression could predict poor OS (HR 3.02, 95% CI: 2.35–3.89, P < 0.01, PFDR < 0.01), MFS (HR 5.22, 95% CI: 2.08–13.08, P < 0.01, PFDR < 0.01), and EFS (HR 1.07, 95% CI: 1.03–1.11, P < 0.01, PFDR < 0.01). Subgroup analyses revealed the underlying sources of heterogeneity. Publication bias was observed in the analysis of metastasis. Sensitivity analysis revealed that the results were robust. Our findings indicated that ezrin overexpression was significantly correlated with poor survival and more advanced tumor progression in bone and soft tissue sarcomas, which suggests that ezrin might be a valuable prognostic biomarker and a potential therapeutic target.

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Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival: validatory study of two independent patient cohorts

Cited by 22 publications

References 24 publications

Loss of ezrin in human intrahepatic cholangiocarcinoma is associated with ectopic expression of E‐cadherin

Loss of ezrin in human intrahepatic cholangiocarcinoma is associated with ectopic expression of E‐cadherin

MicroRNA-144 inhibits the proliferation, apoptosis, invasion, and migration of osteosarcoma cell line F5M2

The clinical prognostic significance of ezrin in patients with bone and soft tissue sarcomas: a meta‐analysis

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