表观遗传调节剂UHRF1在胰腺癌中的表达及其临床意义

Expression and clinical significance of epigenetic regulator UHRF1 in pancreatic carcinoma

目的:基于生物信息学进行数据挖掘以探讨UHRF1在胰腺癌中的表达情况及对胰腺癌患者预后的影响。方法:使用GEPIA数据库探索UHRF1在泛癌中的表达模式。应用Kaplan-Meier Plotter分析UHRF1对胰腺癌患者预后的意义。使用UCGA Xena制作热图分析UHRF1的表达水平、甲基化状态和拷贝数变异对胰腺癌患者预后的影响。筛选TCGA数据库和GEO数据库(GSE43795数据集)胰腺癌中UHRF1共表达基因,并应用Metascape进行基因功能富集分析。结果:UHRF1在大部分癌症中差异表达;和正常胰腺组织相比,胰腺癌组织UHRF1表达量显著升高(P<0.01)。Kaplan-Meier Plotter数据平台显示UHRF1高表达显著影响胰腺癌患者预后,其中高、低表达组中位生存期分别为16.6个月和23.17个月(HR=2.03,95%可信区间1.34~3.06,P=0.000 58)。使用UCGA Xena平台对来自TCGA数据库的178个胰腺癌数据进行分析显示,UHRF1 mRNA表达水平和胰腺癌患者预后相关,但甲基化状态以及拷贝数变异和胰腺癌患者的总生存率没有明显相关性。通过分析得出UHRF1与KIF11、KIF23、RRM2、ERCC6L和MELK等基因具有共表达关系,并且富集分析显示UHRF1共表达基因与细胞核分裂以及细胞周期相变等密切相关。在HPA数据库中分析胰腺肿瘤组织与正常组织UHRF1的免疫组化染色结果,显示UHRF1蛋白在正常胰腺组织中未检测到,而在胰腺癌组织中高表达。结论:胰腺癌组织中UHRF1基因表达水平显著上调,且UHRF1过表达对胰腺癌患者预后不利,UHRF1可能通过参与细胞核分裂以及细胞周期等过程实现对胰腺癌的影响。UHRF1可能作为胰腺癌预后的重要预测指标,并有潜力成为胰腺癌治疗的靶标。

Objective: To investigate the expression of UHRF1 in pancreatic carcinoma and its prognostic significance by using bioinformatics data mining technology. Methods: GEPIA database was used to explore UHRF1 expression in Pan-cancer. Prognostic significance of UHRF1 was analyzed by Kaplan-Meier Plotter. UCGA Xena was used to analyze the UHRF1 expression level, methylation and copy number variation on prognosis of pancreatic carcinoma patients. UHRF1 co-expressing genes were screened from TCGA database and GEO database(GSE43795), and Metascape was applied to analyze the gene function enrichment. Results: UHRF1 expressed differently in most cancers and UHRF1 expression increased significantly in pancreatic carcinoma tissues as compared with normal tissues(P<0. 01). Kaplan-Meier Plotter analysis demonstrated that the overall survival time of the high and low UHRF1 expression groups were 16. 6 months and 23. 17 months, respectively, with significant difference(HR=2. 03, 95%CI:1. 34-3. 06;P=0. 000 58). Analysis of 178 pancreatic carcinoma data from TCGA database using UCGA Xena platform showed that UHRF1 mRNA expression level correlated with the prognosis of pancreatic carcinoma patients, but methylation and copy number variation had no significant correlation. UHRF1 was correlated with KIF11, KIF23, RRM2, ERCC6 L,and MELK genes and enrichment analysis showed that UHRF1 co-expressing genes were closely correlated with mitotic nuclear division and cell cycle phase transition. Immunohistochemical staining of UHRF1 showed that UHRF1 protein was not detected in normal pancreatic tissues but overexpressed in pancreatic carcinoma tissues. Conclusion: UHRF1 gene expression level was significantly upregulated in pancreatic carcinoma and UHRF1 overexpression was unfavorable for prognosis of pancreatic carcinoma patients. UHRF1 might be used as an important predictor of pancreatic carcinoma prognosis and could be used as target for treatment.