EZH2和VEGF在结直肠癌中的表达其与患者预后关系生物信学分析及验证  

Relationship between EZH2 and VEGF expression and prognosis in colorectal cancer

作　　者：于立刚 陈素琴 毛国良 

机构地区：[1]天津武清区人民医院普通外科 [2]天津武清区人民医院病理科

出　　处：《世界华人消化杂志》2020年第5期155-166,共12页World Chinese Journal of Digestology

基　　金：天津市武清区科技计划项目资助,No.WQKJ201738~~

摘　　要：背景结直肠癌(colorectal carcinoma, CRC)是临床上常见的消化系统恶性肿瘤.但其确切发病机制和预后独立因素仍未阐明.本研究通过生物信息学方法分析了zeste基因增强子同源物2(enhancerofzestehomolog2,EZH2)和血管内皮生长因子(vascular endothelial growth factor, VEGF)基因在CRC中的表达情况及其和患者预后的感谢.并采用免疫组化检测了EZHE2和VEGF蛋白的表达情况及其与患者临床特征的关系.目的探讨EZH2和VEGF在CRC中的表达、突变情况及其与患者临床病理特征和预后的关系.方法首先在TCGA数据库中比较EZH2和VEGF基因mRNA在肠癌患者癌和癌旁组织中的表达,同时分析EZH2和VEGF基因的突变情况;采用STRING数据库建立EZH2和VEGF基因表达网络并筛选网络中的关键基因.根据EZH2和VEGF在肿瘤组织中的表达分为高低表达组, Cox回归模型Log-rank检验比较高低表达组患者总生存和无疾病进展生存是否存在差异.同时选取80例肠癌手术患者,留取患者癌组织和癌旁组织,采用免疫组织化学法检测上述组织中EZH2和VEGF蛋白表达水平.结果 TCGA数据库显示EZH2和VEGF基因在CRC组织中的表达水平显著高于对应的正常肠上皮组织(P <0.05),而与肠癌患者的临床分期并无明显相关性(P>0.05);EZH2和VEGF基因在人肠癌中的突变率分别为1.5%和1.9%,且EZH2和VEGF不同突变组织中mRNA表达水平存在明显差异.网络中共有22个蛋白,各蛋白平均相互作用指数为10.5,区域聚集指数为0.8,各蛋白富集明显(P<0.01). Cytohubb软件筛选出EZH2, DNMT1, HDAC2, YY1和SUZ12为网络中的关键基因;EZH2和VEGF高低表达与患者总生存期均无相关性(P>0.05),而VEGF高表达组患者无疾病进展生存期显著低于低表达组(HR=1.8, P<0.05).免疫组化显示, EZH2和VEGF在肠癌组织中的阳性表达率均显著高于癌旁组织(P<0.01).EZH2阳性表达与肠癌肿瘤直径、分化程度和Duke分期有关(P<0.05).而VEGF阳性表达�BACKGROUND Colorectal cancer(CRC) is a common malignant tumor of the digestive system. However, its exact pathogenesis and independent prognostic factors are still unclear. In this study, we analyzed the expression of enhancer of zeste homolog 2(EZH2) and vascular endothelial growth factor(VEGF) genes in CRC by using bioinformatics method and their relationship with prognosis. The expression of EZHE2 and VEGF proteins and their relationship with the patients’ clinical characteristics were detected by immunohistochemistry.AIM To investigate the expression and mutation status of EZH2 and VEGF in CRC and their relationship with clinicopathological features and prognosis. METHODS The expression of EZH2 and VEGF genes in CRC and tumor adjacent tissues was compared in the TCGA database, and the mutations of EZH2 and VEGF genes were analyzed. The expression network of EZH2 and VEGF genes was established with the STRING database and the key genes in the network were screened. According to the expression of EZH2 and VEGF in tumor tissues, the patients were divided into high and low expression groups. Cox regression model and logrank test were used to compare the difference of total survival and disease-free survival between the high and low expression groups. In addition, 80 patients with CRC who underwent surgery were selected, and their cancer tissues and adjacent tissues were collected. The expression of EZH2 and VEGF proteins in the above tissues was detected by immunohistochemistry.RESULTS Analysis based on the TCGA database showed that the expression levels of EZH2 and VEGF genes in CRC tissues were significantly higher than those in matched normal intestinal epithelial tissues(P < 0.05), but they had no significant correlation with clinical stage of CRC(P > 0.05).The mutation rates of EZH2 and VEGF genes in human CRC were 1.5% and 1.9%, respectively, and there were significant differences in the expression levels of EZH2 and VEGF m RNA in tissues with different EZH2 and VEGF mutation statuses. There are 22 protei

关 键 词：肠癌 EZH2基因 VEGF基因 预后 免疫组化 

分 类 号：R735.3[医药卫生—肿瘤]