Ephrin-A4 Ligand (EFNA4) Predicts Poor Prognosis of Hepatocellular Carcinoma and Promotes Tumor Proliferation

Background/Aims: Primary hepatocellular carcinoma (HCC) is one of the most lethal tumor diseases in the world. Receptor tyrosine kinases (RTKs) are thought to play a vital role in HCC and Ephrin-A4 ligand (EFNA4) is a membrane-bound molecule that can activate RTKs through erythropoietin-producing hepatocellular (Eph) receptors. However, the specific role of EFNA4 remains unknown. The aim of our study was to explore the prognostic value of EFNA4 expression in HCC. Methods: Bioinformatics analyses were conducted to probe the expression levels and prognostic value of EFNA4 in HCC. The quantitative real-time polymerase chain reaction, immunohistochemical and western blot were used to confirm the expression of EFNA4 in paired clinical specimens of HCC. Colony formation assay was used to confirm the proliferation of tumor cell. Results: The expression of EFNA4 is generally elevated in various cancers. Especially, EFNA4 was upregulated in tumor tissue and associated with clinical stage in HCC patients. HCC patients with lower levels of EFNA4 possessed better survival and progression-free survival times. Colony formation assay indicated that the overexpression of EFNA4 promoted tumor cell proliferation. Conclusion: These results demonstrated that EFNA4 played as an oncogenic gene and a prognostic biomarker for HCC patients. ( J CLIN EXP HEPATOL 2023;13:767-773)