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

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.