A Comprehensive Analysis of Epoxide Hydrolase 2 (EPHX2) in Pan-Cancer

Abstract

Background and Aims

Epoxide hydrolase 2 (EPHX2) regulates lipid signaling across various metabolites by encoding soluble epoxide hydrolase. However, its mechanisms and implications in human malignancies remain unknown. This research aimed to detail the prognostic landscape of EPHX2 in pan-cancer and explore its potential relationship with immune infiltration in the tumor microenvironment.

Methods

Herein, multiple bioinformatics tools were used to comprehensively evaluate the expression, diagnostic, and prognostic significance of EPHX2 and its roles in the tumor immune microenvironment in human cancers. The underlying EPHX2-associated signaling pathways in cancers were investigated by gene set variation analysis (GSVA). TIDE, GDSC, and CTRP databases were applied to predict the response of EPHX2 to immunotherapy and sensitivity to small molecule drugs. Furthermore, EPHX2 expression was also validated by qPCR experiments in various cancer cell lines.

Results

Overall results revealed significant down-regulation of EPHX2 mRNA expression in most tumors. Despite its high predictive significance across cancers, EPHX2 played a protective or detrimental effect in distinct types of cancers. EPHX2 proved to be a valuable diagnostic biomarker in a range of tumor types, particularly in kidney renal clear cell carcinoma, cervical squamous cell carcinoma, and endocervical adenocarcinoma. Genetic alterations of EPHX2 in 33 tumors were also investigated. EPHX2 expression was significantly linked to immune cell infiltrations (particularly tumor-associated macrophages), tumor mutation burden, microsatellite instability, immune modulators, and immunotherapeutic biomarkers. Single-cell sequencing and GSVA highlighted the relevance of EPHX2 in regulating various cancer-related biological processes, including cell cycle and apoptosis. In this view, targeting EPHX2-dependent signaling could be a promising therapeutic strategy for tumor immunotherapy.

Conclusion

EPHX2 may serve as a potential molecular biomarker for diagnosis and prognosis in pan-cancer and could become a novel therapeutic target for various cancers.