Overexpression of WAVE3 promotes tumor invasiveness and confers an unfavorable prognosis in human hepatocellular carcinoma

• Published in: Biomedicine & pharmacotherapy 2015-02, Vol.69, p.409-415
• Main Authors: Ji, Yingjie, Li, Bing, Zhu, Zhenyu, Guo, Xiaodong, He, Weiping, Fan, Zhenping, Zhang, Wenjin
• Format: Article
• Language: English
• Subjects: Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Female; Gene Knockdown Techniques; Hep G2 Cells; Hepatocellular carcinoma; Humans; Immunohistochemistry; Internal Medicine; Kaplan-Meier Estimate; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Medical Education; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Prognosis; Proportional Hazards Models; Protein Transport; Small interfering RNA; Subcellular Fractions - metabolism; Wiskott-Aldrich Syndrome Protein Family - metabolism; Wiskott-Aldrich syndrome verprolin-homologous 3
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2014.11.001

Abstract Background Wiskott-Aldrich syndrome verprolin-homologous (WAVE) 3 has been reported to be implicated in various malignant tumors, but its role in hepatocellular carcinoma (HCC) remains elusive. The aim of this study was to investigate the effect of WAVE3 on the behaviors of HCC cells and to evaluate its clinical impact. Materials and methods A total of 120 paired of HCC and adjacent non-cancerous tissues were used to detect expression pattern of WAVE3 by immunohistochemistry. Then, the associations of WAVE3 expression with clinicopathologic characteristics and patients’ prognosis were examined. The roles of WAVE3 in migration and invasion of HCC cell line HepG2 were also evaluated in vitro. Results Positive immunostaining of WAVE3 protein was predominantly observed in the cytoplasm of HCC cells. Compared to adjacent non-cancerous tissues, the expression levels of WAVE3 protein were significantly upregulated in HCC tissues ( P < 0.001). Additionally, high WAVE3 expression was significantly associated with advanced tumor stage ( P = 0.008) and positive distant metastasis ( P = 0.001). Then, high WAVE3 expression correlated significantly with poor prognosis, and WAVE3 status was identified as an independent significant prognostic factor. Moreover, small interfering RNA targeting WAVE3 was used to inhibit the expression of WAVE3 in HepG2 cells. We found that suppression of WAVE3 could inhibit migration and invasion of HepG2 cells. Conclusion Our clinical study have characterized WAVE3 as biomarker for HCC progression and metastasis, and more importantly, have identified it as an independent prognostic marker for HCC patients. Our data also indicated that WAVE3 is pivotal in controlling oncogenic phenotypes of human HCC cells.