EPHX2 Overexpression Deters the Advancement of Clear Cell Renal Cell Carcinoma via Lipid Metabolism Reprogramming

Bo Guan¹Cong Huang^2*Jun He²Weimin Shan¹Di Cui³Xiaowei Li¹Chaozhao Liang²Zongyao Hao²

• ¹Fuyang City People's Hospital, Fuyang, Anhui Province, China
• ²First Affiliated Hospital of Anhui Medical University, Hefei, China
• ³Fuyang Normal University, Fuyang, Anhui Province, China

Clear cell renal cell carcinoma (ccRCC) is a prevalent and aggressive variant of renal cancer, representing approximately 80% of all renal cell carcinoma instances. Its insidious onset and absence of early symptoms can lead to misdiagnosis or delayed treatment. Over recent decades, there has been a notable annual increase in its incidence. The highly malignant characteristics and poor prognosis of ccRCC present significant challenges within clinical practice. EPHX2, an metabolic regulator with tumor-suppressive properties belonging to the epoxide hydrolase family, not only influences cell cycle dynamics but also interacts with various signaling pathways to inhibit tumor growth. To elucidate the precise function of EPHX2 in the progression of clear cell renal cell carcinoma, we employed a comprehensive strategy involving transcriptome analysis, single-cell RNA sequencing, machine-learning model development, as well as functional assessments including analyses of cell proliferative, migratory, and invasion. Our findings revealed a marked down-regulation of EPHX2 expression in ccRCC tumor tissues in comparison to normal renal tissues (P < 0.001).Moreover, EPHX2 overexpression significantly restrained the proliferative, migratory, and invasive capacities of ccRCC cell lines. Although this study is limited by a relatively small sample size and necessitates further longitudinal clinical validation, it provides robust evidence that EPHX2 significantly influences the progression of ccRCC and underscores its potential as a therapeutic target.