EPHX2 Expression and Its Association with Prognosis, Metabolic Regulation, and Metastasis-Related Pathways in Lung Adenocarcinoma

Background/Objectives: Epoxide hydrolase 2 (EPHX2), which encodes soluble epoxide hydrolase (sEH), is involved in arachidonic acid metabolism and has been associated with inflammation, lipid metabolism, and tumor biology. However, its prognostic significance and biological associations in lung adenocarcinoma (LUAD) remain unclear. This study aimed to investigate the expression profile, prognostic value, and molecular pathways of EPHX2 in LUAD using bioinformatics analyses. Methods: EPHX2 expression was evaluated using TNMplot, GEPIA2, and GEO datasets, while protein expression was assessed using the Human Protein Atlas and CPTAC/UALCAN platforms. Prognostic analyses were performed using Kaplan–Meier Plotter, GEPIA2, and Human Protein Atlas datasets. Co-expression and gene set enrichment analyses were conducted using LinkedOmics, and functional enrichment analyses were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome databases. Correlation and protein–protein interaction (PPI) analyses were evaluated using GEPIA2 and STRING. Results: EPHX2 expression was significantly reduced in LUAD tissues compared with normal lung tissues across datasets, and these findings were supported at the protein level. High EPHX2 expression was associated with better overall survival and retained independent prognostic significance in multivariate Cox analysis. Functional enrichment analyses demonstrated associations with lipid metabolism, arachidonic acid metabolism, cytochrome P450-related pathways, and oxidative processes. Correlation analyses suggested potential associations between EPHX2 and angiogenesis, extracellular matrix remodeling, and hypoxia-related pathways. Conclusions: Bioinformatics analyses suggest that EPHX2 may participate in metabolic and tumor progression-related regulatory networks and may serve as a prognostic biomarker in LUAD.