Upregulation of EPS8L3 is associated with tumorigenesis and poor prognosis in patients with liver cancer.

Epidermal growth factor receptor kinase substrate 8 (EPS8) plays critical roles in a variety of solid tumors. However, the biologic functions and clinical significance of EPS8-like 3 (EPS8L3), an EPS8-related protein, in liver cancer remain unclear. To measure EPS8L3 expression in liver cancer cell lines, reverse transcription-quantitative PCR and western blot analyses were performed. The correlation between 338 patients with liver cancer and various clinicopathological factors obtained from the Oncomine database were evaluated using the χ² test. Survival of patients with different expression of EPS8L3 was determined using Kaplan-Meier survival analysis with a log rank test, and Cox regression analysis was performed to estimate the prognostic significance of EPS8L3 expression. Additionally, cell proliferation and migration were determined using Cell Counting Kit-8 and wound healing assays. The results revealed that EPS8L3 expression was significantly upregulated in liver cancer tissues and cell lines (P<0.01), and that the expression of EPS8L3 was closely associated with grade (P=0.024) and mortality (P=0.011). Furthermore, survival analysis suggested patients with high EPS8L3 expression exhibited shorter survival compared with those with low EPS8L3 expression. Cox regression analysis indicated that EPS8L3 could be regarded as a prognostic biomarker in patients with liver cancer (hazard ratio, 1.58; 95% confidence interval, 1.085–2.301; P=0.017). Additionally, in vitro assays revealed that EPS8L3 depletion significantly inhibited liver cancer cell proliferation and migration, and reduced the levels of phosphorylated PI3K and AKT in the PI3K/AKT signaling pathway. Collectively, the results of the present study, for the first time to the best of our knowledge, demonstrated that EPS8L3 serves as an oncogene in liver cancer development; therefore, EPS8L3 may be a valuable prognostic predictor for patients with liver cancer. [ABSTRACT FROM AUTHOR]