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Overexpression of RALY promotes migration and predicts poor prognosis in hepatocellular carcinoma

Authors Zhu Z, Zhang Y, Huang CS, Tang Y, Sun C, Ju W, He X

Received 7 August 2018

Accepted for publication 26 September 2018

Published 9 November 2018 Volume 2018:10 Pages 5559—5572

DOI https://doi.org/10.2147/CMAR.S182996

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 6

Editor who approved publication: Dr Beicheng Sun


Zebin Zhu,1–3,* Yixi Zhang,1–3,* Chensong Huang,4 Yunhua Tang,1–3 Chengjun Sun,1–3 Weiqiang Ju,1–3 Xiaoshun He1–3

1Organ Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China; 2Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, Guangdong, China; 3Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou 510080, Guangdong, China; 4Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, China

*These authors contributed equally to this work

Introduction: RALY plays a critical role in promoting invasiveness and is associated with poor prognosis in different types of cancers. However, the prognostic value of RALY and its precise role in hepatocellular carcinoma (HCC) remain unknown.
Materials and methods: We detected the expression of RALY in 127 clinical HCC tissue samples and seven HCC cell lines by immunohistochemical staining and Western blotting. The prognostic value of RALY expression was assessed using the Kaplan–Meier method. The expression and prognostic value of RALY were also studied by bioinformatics analysis of data from the Gene Expression Omnibus and The Cancer Genome Atlas. The biological influence of RALY on HCC cell lines was studied using proliferation, transwell migration, and invasion assays in vitro.
Results: The expression of RALY in HCC tissues was significantly higher than that in adjacent normal liver tissues. Abnormally high expression of RALY was associated with tumor size (P=0.031), TNM stage (P=0.026), presurgical serum AFP levels (P=0.025), and vascular invasion (P=0.001). Kaplan–Meier analysis demonstrated that higher expression of RALY correlated with poorer overall survival and disease-free survival in HCC patients. High RALY expression was an independent adverse prognostic factor for overall survival (HR =2.559, 95% CI: 1.710–3.827, P<0.001) and disease-free survival (HR =2.053, 95% CI: 1.384–3.047, P<0.001) in HCC. Moreover, knockdown of RALY expression using a specific shRNA suppressed the proliferation, migration, and invasion capabilities of HCC cells in vitro. Knockdown of RALY expression in HCC cell lines resulted in upregulation of E-cadherin and downregulation of N-cadherin, vimentin, and snail.
Conclusion: Taken together, our results indicate that RALY represents a biomarker for the prognosis of patients with HCC and highlight the importance of RALY as an oncogene in HCC.

Keywords: RALY, hepatocellular carcinoma, migration, invasion

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