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Expression of OVOL2 is related to epithelial characteristics and shows a favorable clinical outcome in hepatocellular carcinoma

Authors Fu H, Qi L, Chen L, He Y, Zhang N, Guo H

Received 12 April 2016

Accepted for publication 6 July 2016

Published 29 September 2016 Volume 2016:9 Pages 5963—5973


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Cho

Hui Fu,1,2,* Lisha Qi,2,3,* Lu Chen,1,2 Yuchao He,1,2 Ning Zhang,1,2 Hua Guo1,2

1Department of Tumor Cell Biology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, 2The Key Laboratory of Tianjin Cancer Prevention and Treatment, National Clinical Research Center for Cancer, 3Department of Pathology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China

*These authors contributed equally to this work

Abstract: Metastasis involves epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition. Ovol2 belongs to the Ovo-like family (Ovol) of evolutionarily conserved zinc-finger transcription factors that regulate gene expression in various differentiation processes. Recent studies have demonstrated that Ovols affect mesenchymal–epithelial transition by inducing the expression of miR-200 in a range of human cancers. Downregulated Ovol2 expression is involved in the invasion and metastasis of breast and prostate cancers, but little is known about its expression and prognostic value in other cancers, including hepatocellular carcinoma (HCC). This study was designed to explore the clinical and prognostic significance of Ovol2 in patients with HCC. The expression of Ovol2 in tumor samples from patients with HCC and HCC cell lines was examined using Western blotting, real-time polymerase chain reaction, and immunohistochemistry. The expression levels of EMT-related markers, including E-cadherin, N-cadherin, and vimentin, were detected in relation to Ovol2 expression. The prognostic significance of Ovol2 in patients with HCC was statistically analyzed by Kaplan–Meier and Cox regression analyses. Ovol2 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues. Low expression of Ovol2 was detected in HCC tissues with poor histological differentiation, microvascular invasion, and cirrhosis. A significant relationship was observed between Ovol2 and EMT marker expression levels. Kaplan–Meier analysis showed that overall survival was significantly worse in patients with HCC with low Ovol2 expression, indicating that Ovol2 deletion was an independent predictor of unfavorable prognosis in patients with HCC. Elevated Ovol2 expression may suppress HCC cell invasion and metastasis via restricting EMT.

Keywords: Ovol2, hepatocellular carcinoma, prognosis, epithelial–mesenchymal transition, mesenchymal–epithelial transition

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