摘要
目的通过不同的在线数据集探讨Prefoldin4(PFDN4)在肝细胞癌发生发展中的潜在作用和机制。方法在TCGA和GEO数据库检测PFDN4的表达,然后在蛋白水平和肝细胞癌细胞系中进行验证。表观遗传机制方面,通过MEXPRESS分析PFND4表达水平和启动子甲基化的相关性。利用Metascape对PFDN4高、低表达组间差异基因相关生物功能进行富集并构建蛋白-蛋白互作网络,然后通过Cytoscape筛选相关Hub基因,并进一步构建相应的转录因子-Hub与miRNA-Hub基因网络。结果PFDN4在肝细胞癌中的表达增加,并通过多个数据库(TCGA、GEO、HPA和DepMap)得到验证,PFDN4表达和启动子CpG位点(54207873)甲基化负相关。DESeq2分析发现,PFDN4高、低表达组间有552个的差异基因。Metascape富集发现PFDN4表达水平可调节上皮细胞分化、胚胎器官发育、肺上皮发育以及交配和鞘脂类生物合成过程。PPI网络的MCOD分析发现有8个显著的基因簇,其相关生物学功能主要与GPCR信号通路和上皮细胞分化相关。肝细胞癌中PFDN4表达相关的10个Hub基因为NTS、HTR2B、ADRA1A、TAC1、TACR3、GRPR、CCKBR、KISS1R、PROK1和CYP3A4。使用Netwaranyst预测到40个转录因子和38个miRNA可能和Hub基因相互作用。结论PFDN4在肝细胞癌的发生发展中可能起着重要作用,PFDN4表达相关潜在Hub基因、转录因子和miRNA,可进一步用于探索新的诊断和治疗策略。
Objective To explore the potential roles and mechanisms of Prefoldin4(PFDN4)in the development of hepatocellular carcinoma(HCC)through different online datasets.Methods The expression of PFDN4 was detected in TCGA and GEO databases,and then verified at the protein level and in hepatocellular carcinoma cell lines.In terms of epigenetic mechanism,the correlation between PFND4 expression level and promoter methylation was analyzed by MEXPRESS.Metascape was used to enrich the biological functions of differentially expressed genes between PFDN4 high and low expression groups and construct a protein-protein interaction network.Then,the relevant Hub genes were screened by Cytoscape,and the corresponding transcription factor-Hub and miRNA-Hub gene networks were further constructed.Results The expression of PFDN4 in hepatocellular carcinoma was increased and verified by multiple databases(TCGA,GEO,HPA and DepMap).PFDN4 expression was negatively correlated with promoter CpG site(54207873)methylation.DESeq2 analysis showed that there were 552 differential genes between PFDN4 high and low expression groups.Metascape enrichment found that PFDN4 expression level can regulate epithelial cell differentiation,embryonic organ development,lung epithelial development,mating and sphingolipid biosynthesis.The MCOD analysis of PPI network found that there were 8 significant gene clusters,and their related biological functions were mainly related to GPCR signaling pathway and epithelial cell differentiation.The 10 Hub genes associated with PFDN4 expression in hepatocellular carcinoma were NTS,HTR2B,ADRA1A,TAC1,TACR3,GRPR,CCKBR,KISS1R,PROK1 and CYP3A4.Netwaranyst predicted that 40 transcription factors and 38 miRNAs may interact with Hub genes.Conclusion PFDN4 may play an important role in the occurrence and development of hepatocellular carcinoma.PFDN4 expresses potential hub genes,transcription factors and miRNAs,which can be further used to explore new diagnostic and therapeutic strategies.
作者
黄娟君
祝伟
HUANG Juanjun;ZHU Wei(Departments of Infectious Diseases,Ganzhou People's Hospital,Ganzhou 341000,Jiangxi,China;Central Laboratory,Ganzhou People's Hospital,Ganzhou 341000,Jiangxi,China)
出处
《医学信息》
2025年第19期9-16,共8页
Journal of Medical Information
基金
江西省卫健委科技计划项目(编号:202311888)。
