Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Beihua University, Jilin 132001, P.R. China.
Department of Oncology, The First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2019 Sep;20(3):2493-2499. doi: 10.3892/mmr.2019.10471. Epub 2019 Jul 4.
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.
表皮生长因子受体激酶底物 8（EPS8）在各种实体瘤中发挥着关键作用。然而，EPS8 相关蛋白 EPS8 样 3（EPS8L3）在肝癌中的生物学功能和临床意义尚不清楚。为了检测肝癌细胞系中 EPS8L3 的表达，进行了逆转录定量 PCR 和 Western blot 分析。通过 χ2 检验评估了从 Oncomine 数据库获得的 338 例肝癌患者与各种临床病理因素之间的相关性。使用 Kaplan-Meier 生存分析和对数秩检验确定不同 EPS8L3 表达的患者的生存情况，并使用 Cox 回归分析估计 EPS8L3 表达的预后意义。此外，使用细胞计数试剂盒-8 和划痕愈合试验测定细胞增殖和迁移。结果显示，EPS8L3 在肝癌组织和细胞系中表达显著上调（P<0.01），并且 EPS8L3 的表达与分级（P=0.024）和死亡率（P=0.011）密切相关。此外，生存分析表明，高 EPS8L3 表达的患者的生存时间短于低 EPS8L3 表达的患者。Cox 回归分析表明，EPS8L3 可作为肝癌患者的预后生物标志物（危险比，1.58；95%置信区间，1.085-2.301；P=0.017）。此外，体外实验表明，EPS8L3 耗竭显著抑制肝癌细胞增殖和迁移，并降低 PI3K/AKT 信号通路中磷酸化 PI3K 和 AKT 的水平。综上所述，本研究首次表明，EPS8L3 作为一种癌基因在肝癌的发展中起作用；因此，EPS8L3 可能是肝癌患者有价值的预后预测指标。
