基于生物信息学的肝母细胞瘤关键生物标志物的筛选与鉴定  

Screening and Identification of Key Biomarkers of Hepatoblastoma Based on Bioinformatics

作　　者：裴薇[1] 汪鹏刚 刘登瑞[1] 高明太[1] PEI Wei;WANG Peng-gang;LIU Deng-rui;GAO Ming-tai(Department of Pediatric Surgery,the First Hospital of Lanzhou University,Lanzhou 730000,Gansu,China)

机构地区：[1]兰州大学第一医院小儿外科,甘肃兰州730000

出　　处：《医学信息》2023年第11期1-9,15,共10页Journal of Medical Information

摘　　要：目的筛选并鉴定肝母细胞瘤(HB)的关键基因,并进行综合分析。方法从基因表达综合数据库(GEO)中下载人类肝母细胞瘤表达谱基因芯片数据,筛选肝母细胞瘤发生发展相关的候选基因,使用GEO2R筛选出差异表达基因(DEGs),鉴定并进行GO和KEGG功能富集分析,构建蛋白-蛋白相互作用网络(PPI),使用STRING和Cytoscape进行分析。结果共鉴定出DEGs 135个,包括上调基因114个,下调基因21个;共鉴定出ANGPTL3、MT2A等7个关键基因;GO分析显示,DEGs的BP显著富集于生长负调节、离子反应、纤维蛋白溶解、补体激活等过程;MF主要富集于内肽酶活性、受体结合等;CC变化主要富集在细胞外区、膜攻击复合物和胞质囊腔。KEGG通路分析显示,这些差异表达基因主要集中在免疫应答、补体激活途径等。从PPI网络中筛选出与DEGs关系最密切的7个关键基因,包括ANGPTL3、MT2A、ABCB11、MBL2、IGF1、CFH、ADHFE1;总体生存分析显示,ABCB11、MBL2、ADHFE1改变的HB患者总生存率较差,ABCB11、MBL2改变的HB患者显示较差的无病生存期,ABCB11改变与较差的无病生存期显著相关,但与较差的总生存期无关(总生存期P=0.228,无病生存期P=0.0143)。结论共鉴定出135个DEGs和7个关键基因,可作为HB的诊断生物标志物,有助于理解HB发生的分子机制,并可能为理解HB的分子机制提供新的见解。Objective To screen and identify the key genes of hepatoblastoma and make a comprehensive analysis.Methods The gene chip data of human hepatoblastoma expression profile were downloaded from the Gene Expression Omnibus(GEO)database,and the candidate genes related to the occurrence and development of hepatoblastoma were screened.The differentially expressed genes(DEGs)were screened by GEO2R,identified and analyzed by GO and KEGG functional enrichment analysis.The protein-protein interaction network(PPI)was constructed and analyzed by STRING and Cytoscape.Results A total of 135 DEGs were identified,including 114 up-regulated genes and 21 down-regulated genes.A total of 7 key genes including ANGPTL3 and MT2A were identified.GO analysis showed that the BP of DEGs were significantly enriched in the processes of negative growth regulation,ion response,fibrinolysis,complement activation,and so on.MF was mainly enriched in endopeptidase activity and receptor binding.CC changes were mainly enriched in the extracellular region,membrane attack complex,and cytosolic vesicle compartments.KEGG pathway analysis showed that these differentially expressed genes were mainly concentrated in the immune response and complement activation pathways.Seven key genes most closely related to DEGs were screened from the PPI network,including ANGPTL3,MT2A,ABCB11,MBL2,IGF1,CFH and ADHFE1.Overall survival analysis showed that HB patients with changes in ABCB11,MBL2 and ADHFE1 had poor overall survival.HB patients with ABCB11 and MBL2 changes show poor disease-free survival.Alterations in ABCB11 were significantly associated with worse disease-free survival but not overall survival(P=0.228 for overall survival and P=0.0143 for disease-free survival).Conclusion A total of 135 DEGs and 7 hub genes are identified,which can be used as diagnostic biomarkers for HB,help to understand the molecular mechanism of HB,and may provide new insights into the molecular mechanism of HB.

关 键 词：肝母细胞瘤 生物标志物 差异表达基因 蛋白相互作用网络 

分 类 号：R735.7[医药卫生—肿瘤]