Integrative Analysis of EPHX4 as a Novel Prognostic and Diagnostic Biomarker in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, necessitating the identification of novel biomarkers for improved prognosis and diagnosis. This study investigates the role of epoxide hydrolase 4 (<i>EPHX4</i>), a member of the epoxide hydrolase family, in LUAD. Using data sourced from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, which were subsequently validated by the Gene Expression Omnibus (GEO), we analyzed levels of <i>EPHX4</i> expression, mutation, and methylation in tumors versus normal tissues. Our findings revealed a significant upregulation of <i>EPHX4</i> in LUAD tissues compared to normal lung tissues (<i>p</i> < 0.001), correlating with poorer overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). Furthermore, <i>EPHX4</i> exhibited considerable diagnostic potential, as demonstrated by an area under the curve (AUC) of 0.854 in a Receiver Operating Characteristic (ROC) analysis. Notably, <i>EPHX4</i> expression was associated with immune infiltration, specifically Th2 cells, neutrophils, and macrophages, along with immune checkpoint molecules including PD-L1, PD-L2, and TIM-3. Additionally, <i>EPHX4</i> was involved in pivotal tumor-associated pathways, particularly cell cycle regulation. In conclusion, an elevated <i>EPHX4</i> expression is indicative of poorer prognosis in LUAD and may play a role in immune evasion and cell cycle dysregulation, highlighting its potential as a promising biomarker for the diagnosis and prognostic prediction of LUAD.