Huang_2025_Gene_959_149504

BACKGROUND: Epoxide hydrolase-4 (EPHX4) belongs to the epoxide hydrolase enzyme family, but its biological function remains unclear, especially its potential involvement in the development of pancreatic tumours. This research sought to examine the function of EPHX4 in pancreatic adenocarcinoma (PAAD). METHODS: The expression of EPHX4 across cancers was examined through The Cancer Genome Atlas (TCGA). Bioinformatics was employed, leveraging multiple databases to investigate EPHX4 gene expression in pancreatic cancer and its association with survival prognosis, functional enrichment, immune infiltration, tumour mutation load, and drug sensitivity, among other variables. To evaluate EPHX4 expression in PAAD cells, Western blotting and reverse transcription quantitative PCR were used. A series of in vitro functional experiments was performed to assess the proliferation, migration, and invasion of PAAD cells. RESULTS: EPHX4 expression was markedly elevated in a number of malignancies, including PAAD, and was associated with patient sex, clinical stage, and metastasis to the lymph nodes. High EPHX4 expression was significantly associated with a worse outcome in PAAD patients. According to functional and enrichment studies, EPHX4 is involved in many signalling pathways linked to cancer. The study of immune infiltration revealed that EPHX4 was connected to the existence of a variety of immune cells inside the tumour. Our study revealed that EPHX4 knockdown significantly decreased PAAD cell migration, proliferation, and invasion. CONCLUSION: EPHX4 is highly expressed in PAAD and independently predicts poor survival. Functional experiments demonstrate its tumor-promoting effects. Its involvement in multiple cancer-related signaling pathways and immune regulation mechanisms highlights the dual prognostic and therapeutic potential of EPHX4 in PAAD.