基于生物信息学方法探索EZH2在卵巢癌中的表达及临床意义

Exploring the expression and clinical significance of EZH2 in ovarian cancer based on bioinformatics methods

目的通过生物信息学方法分析zeste基因增强子同源物2(EZH2)在卵巢癌组织中的表达,探讨在卵巢癌发展过程中的临床意义和可能的调节网络。方法利用GEPIA数据库分析EZH2在卵巢癌组织的表达及预后情况;UALCAN数据库分析EZH2 mRNA的表达与卵巢癌患者年龄、分级、分期的关系;Kaplan-Meier Plotter数据库分析EZH2表达对预后的影响;cBioPortal工具分析TCGA数据库中卵巢癌EZH2基因突变情况;STRING数据库进行GO聚类分析及蛋白-蛋白相互作用网络分析;仙桃生信工具分析EZH2在卵巢癌中的受试者操作特征曲线。结果与正常卵巢组织相比,EZH2在卵巢癌组织中表达量明显上调(P<0.05);除Ⅱ期卵巢癌患者EZH2表达量高于Ⅳ期的患者外(P<0.05),EZH2 mRNA的表达量与卵巢癌的肿瘤分期及分级无明显相关性(P>0.05);EZH2 mRNA的表达与卵巢癌患者的总生存期(OS)、无病生存期及进展后生存期无明显相关性(P>0.05),与无进展生存期高度相关(P<0.01);在卵巢癌中EZH2基因改变频率为11%,EZH2基因改变对OS无影响(P=0.330);EZH2蛋白质相互作用共表达网络发现EZH2与HDAC1、HDAC2等蛋白质分子存在紧密联系,通过聚类分析发现EZH2可能参与调控细胞周期。结论EZH2在卵巢癌中高表达,并在卵巢癌的免疫浸润中起作用,可能参与调控卵巢的细胞周期,有望成为潜在的治疗靶点。

Objective To analyze expression of enhancer of zeste homolog 2(EZH2)by bioinformatics methods,and to explore the clinical significance and possible regulatory network in the development of ovarian cancer.Methods The expression and prognosis of EZH2 in ovarian cancer were analyzed by GEPIA database.The relationship between EZH2 mRNA expression and patients’age,grade and stage of ovarian cancer was analyzed by UALCAN database.The Kaplan-Meier Plotter database was used to analyze the effect of EZH2 expression on prognosis.EZH2 gene mutation of ovarian cancer in TCGA database was analyzed by cBioPortal tool.GO cluster analysis and protein-protein interaction network analysis were carried out in STRING database.The receiver operating characteristic curve of EZH2 in ovarian cancer was analyzed by Xiantao bioinformatics tool.Results Compared with normal ovarian tissue,EZH2 was significantly up-regulated in ovarian cancer tissues(P<0.05).The expression level of EZH2 mRNA in stageⅡovarian cancer patients was higher than that in stageⅣpatients(P<0.05),but there was no obvious correlation between the expression level of EZH2 mRNA and the tumor stage and grade of ovarian cancer(P>0.05).The expression level of EZH2 mRNA was not significantly associated with the overall survival(OS),disease-free survival and post progression survival in ovarian cancer patients(P>0.05),but highly correlated with progression free survival(P<0.01).The frequency of EZH2 gene alteration in ovarian cancer was 11%,and EZH2 gene alteration had no effect on OS(P=0.330).EZH2 protein interaction co-expression network found that EZH2 was closely related to protein molecules such as HDAC1 and HDAC2,and cluster analysis showed that EZH2 might be involved in the regulation of cell cycle.Conclusion EZH2 is highly expressed in ovarian cancer and plays a role in the immune infiltration of ovarian cancer,which may be involved in the regulation of ovarian cell cycle and is expected to be a potential therapeutic target.