环氧化物水解酶2在肝细胞癌中的表达水平与功能作用

本研究通过公共数据和实验数据,全面分析环氧化物水解酶2(epoxide hydrolase 2, EPHX2)在肝细胞癌中的表达情况、功能作用以及预后意义。利用GEO和MitoCarta数据集,筛选肝细胞癌中呈差异表达的线粒体相关基因;利用TCGA数据库分析EPHX2及其相关基因在肝细胞癌中的表达水平;运行R包绘制Kaplan-Meier生存曲线和功能富集分析;基于STRING和GSEA构建蛋白质互作网络和基因集富集分析;荧光定量PCR和GEO数据集验证EPHX2在肝细胞癌中的表达水平。本研究共筛选得到15个在肝细胞癌中呈差异表达的线粒体相关基因。EPHX2在肝细胞癌组织中的表达水平显著降低(P<0.01)。EPHX2表达水平与肝癌患者性别、分期和级别有关,而与年龄、T分期等因素无关。与EPHX2低表达组肝癌患者相比,EPHX2高表达组肝癌患者预后较好。功能富集结果显示,EPHX2与补体途径、脂肪酸降解等信号通路有关。蛋白质互作网络结果显示,EPHX2与HAO1、AGXT、ACOX1、GSTκ1、SCP-2、CAT、CYP2C8,CYP2C9,CYP2B6,和CYP2J2等密切相关。GSEA结果显示,EPHX2低表达组与肝癌细胞增殖、肝癌复发等基因集正相关。荧光定量PCR和GEO数据集验证结果显示,EPHX2在肝细胞癌组织和肝癌细胞株中呈显著低表达。EPHX2在肝细胞癌中呈显著低表达,提示其可能在肝细胞癌发生发展过程中发挥抑癌基因作用,但具体作用机制还需进一步验证。

The Expression and Functional Roles of Epoxide Hydrolase 2 in Hepatocellular Carcinoma

The expression, function and prognostic significance of epoxide hydrolase 2 (EPHX2) in hepatocellular carcinoma (HCC) were comprehensively analyzed through collecting HCC tissues and public database. The GEO and MitoCarta databases were used to identify the mitochondria-related differentially expressed genes (DEGs) in HCC. The Cancer Genome Atlas (TCGA) database was applied to analyze the expression levels of DEGs in HCC, including EPHX2 and its co-expressed genes. The R package was applied to draw the Kaplan-Meier survival curve and gene function enrichment analysis. The STRING database and GSEA software were used to analyze the protein-protein interaction (PPI) network and gene set enrichment analysis. qPCR and GEO database were applied to verify the expression level of EPHX2 in HCC. In the present study, a total of 15 mitochondria-related DEGs were identified in HCC. The expression of EPHX2 in HCC was significantly decreased compared to the normal liver tissues (P<0.01). The expression of EPHX2 was related to gender, tumor stage and grade in HCC, but not associated with age, T stage, et al in HCC. Moreover, compared with the patients with lower expression of EPHX2, patients with higher expression of EPHX2 had a better prognosis. EPHX2 was associated with fatty acid degradation. In addition, PPI results indicated that HAO1, AGXT, ACOX1, GSTκ1, SCP-2, CAT, CYP2C8, CYP2C9, CYP2B6, and CYP2J2 were co-expressed with EPXH2 in HCC. Furthermore, GSEA results showed that the group with lower expression of EPHX2 was positively correlated with the gene set of liver cancer cell proliferation and liver cancer recurrence. qPCR and GEO database results verified that the expression of EPHX2 was significantly decreased in HCC. The expression of EPHX2 was decreased in HCC, strongly suggesting that EPHX2 might function as a tumor suppressor gene in HCC. However, the potential mechanism of EPHX2 in HCC needs to be further verified.