ETS1-Mediated Control of EFNA4 in Gastric Cancer: Effects on Epithelial-Mesenchymal Transition and Cancer Immune Response

Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide, with complex molecular mechanisms driving its development and progression. The PI3K-Akt signaling pathway is known to be dysregulated in various cancers, including GC. In this research, our objective was to explore the relationship between EFNA4 and ETS1 in GC and assess their interconnections with relevant signaling cascades and immune system components. Utilizing publicly accessible datasets, we conducted bioinformatic analyses to evaluate the expression profiles, functional roles, and prognostic significance of EFNA4 and ETS1 in the context of GC. We conducted consensus clustering on 373 TCGA-STAD specimens, utilizing the expression matrix of EFNA4 and ETS1, which resulted in the segregation of samples into two distinct clusters. To evaluate immune infiltration, we employed analytical techniques such as ESTIMATE, CIBERSORT, and ssGSEA to investigate the relationship between these two clusters concerning tumor purity, immune checkpoints, and various immune cell populations. Our findings demonstrated a negative correlation between EFNA4 and ETS1 expression in GC tissues, with distinct roles of EFNA4 in cell differentiation and signaling pathways, while ETS1 played a key role in modulating tumor immunity. Additionally, we performed experimental validation using dual-luciferase reporter assays to investigate the potential regulatory effects of ETS1 on EFNA4 transcription. Our study provides novel insights into the roles of EFNA4 and ETS1 in GC pathogenesis and tumor immunity, highlighting their potential as prognostic markers and therapeutic targets for gastric cancer.