Role of EPS8L3 Upregulation in Liver Cancer

Researchers recently reported that the upregulation of EPS8L3 is associated with tumorigenesis and poor prognosis in patients with liver cancer. The authors were aware that epidermal growth factor receptor kinase substrate 8 (EPS8) plays a number of critical roles in various aspects of solid tumor growth. However, there was insufficient data on the biologic functions and clinical significance of EPS8-like 3 (EPS8L3), an EPS8-related protein, in liver cancer.

A great deal of recent research prompted this study, namely the body of evidence showing that abberant activation of the PI3K/AKT signaling pathway is involved in solid tumor progression of many varieties, by regulating proliferation, differentiation, apoptosis and survival. Liver cancer has been among the indicated malignancies, and it was discovered that EPS8 was a signaling molecule that played a role in regulating the PI3K/AKT signaling pathway.(34,35)

In order to measure EPS8L3 expression in liver cancer cell lines, investigators analyzed reverse transcription-quantitative PCR and performed western blot tests. They subsequently analyzed the correlation between 338 liver cancer patients and, using the χ2 test, compared with clinicopathological factors listed in the Oncomine database. They employed Kaplan-Meier survival analysis with a log rank test, and Cox regression analysis to detrmine how different EPS8L3 expressions influenced patient prognosis and survival. They also calculated cell proliferation and migration via Cell Counting Kit-8 and performed wound healing assays.

They learned that in liver cancer tissues and cell lines, EPS8L3 expression was significantly upregulated (P<0.01), and that EPS8L3 expression was closely associated with grade (P=0.024) and mortality (P=0.011). A survival analysis indicated that patients with high EPS8L3 expression did not survive as long as patients with lower expression of EPS8L3. Cox regression analysis showerd that in liver cancer patients, EPS8L3 served as a prognostic biomarker (hazard ratio, 1.58; 95% confidence interval, 1.085‐2.301; P=0.017). Furterhmore, in vitro assays demonstrated that EPS8L3 depletion strongly inhibited the proliferation and migration of liver cancer cells, and that this depletion also reduced levels of phosphorylated PI3K and AKT in the PI3K/AKT signaling pathway.

The researchers concluded that EPS8L3 was also associated with aggressive clinical outcomes, including higher grade of tumor, a higher mortality rate, and worse prognosis.

Overall, results of the study provided new evidence that EPS8L3 acts as an oncogene in the development of liver cancer. As a result, EPS8L3 appears to be a valuable prognostic tool in the patient with liver cancer.

To substantiate these results, researchers will want to perform western blot analyses or immunohistochemistry panels to monitor EPS8L3 expression in the clinical setting.