EFNA3 Can Serve as Potential Prognostic Biomarker for Luad Patients: A Comprehensive Analysis of the Eph/Ephrin  Family

Abstract Background: Ephrin receptors (Eph) and their ligands called ephrins, function in various disease processes. However, the specific mechanism of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear.Methods: Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. The Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Clinical LUAD tissue was analyzed by immunohistochemistry identifying the clinical value of identifying the ephrin-A3 protein. Weighted Co-expression Network Analysis (WGCNA) and Gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3.Results: EPHA10, EFNA3/4/5 and EPHB1/2 mRNA expression levels were significantly increased in LUAD. EFNB1/2 and EPHB6 expression levels were significantly decreased. Prognostic analysis showed that EFNA3, EFNB1/2, and EPHB2 expression were significant correlate with both overall survival (OS) and progression-free survival (PFS) in LUAD patients. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated as an independent risk prognosis factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. Additionally, higher expression of EFNA3 was significantly correlated with OS in pan-cancer patients.Conclusions: This study revealed the abnormal expression and prognostic value of Eph/Ephrin family members in LUAD. In addition, it is emphasized that EFNA3 may be a novel biomarker for the diagnosis and prognosis of LUAD patients.