基于生物信息学分析FBXO45蛋白在胰腺导管腺癌中的表达及其临床意义

Expression and clinical significance of FBXO45 in pancreatic cancer based on bioinformatics analysis

目的探讨FBXO45蛋白变异对胰腺导管腺癌预后的影响,FBXO45蛋白参与胰腺导管腺癌发生发展的可能作用机制。方法GEPIA数据库在线分析FBXO45 mRNA在不同肿瘤中的表达,UALCAN在线分析FBXO45 mRNA在胰腺导管腺癌中与正常胰腺组织中的表达差异,进一步GEPIA数据库扩大正常胰腺组织对比标本数目,分析FBXO45 mRNA在胰腺导管腺癌中与正常胰腺组织中的表达差异,分析FBXO45基因表达与胰腺导管腺癌患者无病生存期(Disease-free survival,DFS、总生存期(Overall Survival,OS)的关系。Human Protein Atlas数据库中确定FBXO45蛋白在细胞中的定位表达,并检索FBXO45蛋白在胰腺导管腺癌与正常胰腺组织中的表达差异,分析FBXO45蛋白的表达与胰腺导管腺癌患者生存的关系。在cBioPortal数据库中检索FBXO45基因在胰腺癌中的改变,并分析FBXO45基因变异与胰腺导管腺癌预后的关系。从String数据库中分析FBXO45蛋白在信号转导中关系密切的蛋白网络,探讨可能的作用机制。结果GEPIA数据库在线分析FBXO45 mRNA在24种恶性肿瘤中的表达不同,胰腺导管腺癌组织FBXO45基因的表达明显高于正常胰腺组织(P<0.05),FBXO45 mRNA表达水平与胰腺癌患者的无病生存期(DFS)、总生存期(OS)显著相关(P<0.05)。Human Protein Atlas数据库分析结果显示,FBXO45蛋白主要表达于细胞的细胞质中,FBXO45蛋白在胰腺癌组织中显著表达增高(P<0.05),通过生存分析进一步证明高表达FBXO45蛋白的胰腺导管腺癌患者总生存期较差(P<0.05)。在cBioPortal数据库中分析显4%(7/175)的胰腺导管腺癌患者表现出FBXO45基因改变,FBXO45基因变异的患者总生存预后较差(P<0.05)。String数据库显示在PPI网络中与FBXO45蛋白相互作用的蛋白有MYCBP2、TP73、SKP1、CUL1、SPRYD3、KCTD6、MAP3K12、MPP3、UNC13A、UNC13B等。结论FBXO45蛋白在胰腺癌组织中呈现高表达,与患者预后显著相关。FBXO45基因变异的患者总生存预后较差。FBXO45基因变异的患者总生存预后较差,与FBXO45相互作用比较密切的前3位蛋白有MYCBP2、TP73、SKP1,FBXO45蛋白参与蛋白质泛素化途径,是蛋白质修饰的一部分,推测FBXO45通过基因变异、促进蛋白泛素化,在胰腺癌的发生发展中起重要作用,影响其预后。

Objective To explore the effect of its variation on the prognosis of pancreatic ductal adenocarcinoma was determined.To explore the possible mechanism of FBXO45 protein involved in the development of pancreatic ductal adenocarcinoma.Methods GEPIA database online analysis of FBXO45 mRNA expression in different tumors,UALCAN online analysis of FBXO45 mRNA expression difference in pancreatic ductal adenocarcinoma and normal pancreatic tissue,further GEPIA the database to expand the number of normal pancreatic tissue contrast specimens,analysis of the difference in expression between pancreatic ductal adenocarcinoma and normal pancreatic tissue,analysis the relationship of FBXO45 gene expression and the disease-free survival(DFS)、total survival(OS).Human Protein Atlas location expression of FBXO45 protein in cells was determined in the database,and the difference of FBXO45 protein expression in pancreatic ductal adenocarcinoma and normal pancreatic tissue was retrieved.The relationship between the expression of FBXO45 protein and the survival of pancreatic ductal adenocarcinoma patients was analyzed.The changes of FBXO45 genes in pancreatic cancer were retrieved in cBioPortal database and the relationship between FBXO45 gene variation and prognosis of pancreatic ductal adenocarcinoma was analyzed.FBXO45 analysis from String database to explore possible mechanisms of action.Results GEPIA expression of FBXO45 genes in pancreatic ductal adenocarcinoma tissues was significantly higher than that in normal pancreatic tissues(P<0.05).FBXO45 mRNA expression levels were significantly associated with diseasefree survival(DFS)and overall survival(OS)in pancreatic cancer patients(0.05).The results of Human Protein Atlas database analysis showed that FBXO45 protein was mainly expressed in the cytoplasm of cells,and the expression of FBXO45 protein was significantly increased in pancreatic cancer tissues The survival of patients with pancreatic ductal adenocarcinoma with high expression of FBXO45 protein was P<(0.05).The analysis of 4%(7/175)of pancreatic ductal adenocarcinoma in cBioPortal database showed FBXO45 gene changes,and the total survival prognosis of patients with FBXO45 gene variation was poor(P<0.05).String database shows MYCBP2、TP73、SKP1、CUL1、SPRYD3、KC of proteins interacting with FBXO45 proteins in PPI networks TD6、MAP3K12、MPP3、UNC13A、UNC13B etc.Conclusion FBXO45 protein showed high expression in pancreatic cancer tissue,which was significantly related to the prognosis of patients.FBXO45 the total survival prognosis of patients with gene variation is poor.the total survival prognosis of patients with FBXO45 gene variation is poor.the top three proteins with close interaction with FBXO45 have MYCBP2、TP73、SKP1,FBXO45 proteins involved in the protein ubiquitination pathway and are part of protein modification.it is speculated that FBXO45 play a role in the occurrence and development of pancreatic cancer and affect its prognosis through gene variation and promoting protein ubiquitination.