基于生物信息学研究IGFBP在肝癌中表达及其预后价值  

Expression of IGFBP in hepatocellular carcinoma based on bioinformatics study and its prognostic value

作　　者：戴斌 王再兴 马丹丹 金炜东 张智勇 王德盛 Dai Bin;Wang Zaixing;Ma Dandan;Jin Weidong;Zhang Zhiyong;Wang Desheng(Department of Hepatobiliary Surgery,Wuhan No.1 Hospital,Wuhan 430022,China;Department of General Surgery,Taikang Tongji(Wuhan)Hospital,Wuhan 430000,China;Department of General Surgery,General Hospital of Central Theater Command of Chinese People's Liberation Army,Wuhan 430070,China;Department of Hepatobiliary,Pancreatic and Splenic Surgery,Xijing Hospital of Air Force Medical University,Xi'an 710032,China)

机构地区：[1]武汉市第一医院肝胆外科,430022 [2]泰康同济(武汉)医院普通外科,武汉430000 [3]中国人民解放军中部战区总医院普通外科,武汉430000 [4]空军军医大学西京医院肝胆胰脾外科,西安710032

出　　处：《中华肝脏外科手术学电子杂志》2020年第6期602-608,共7页Chinese Journal of Hepatic Surgery(Electronic Edition)

基　　金：湖北省卫生健康委员会联合基金项目(WJ2019H104)。

摘　　要：目的通过生物信息学分析探讨胰岛素样生长因子结合蛋白(IGFBP)家族成员在肝细胞癌(肝癌)中表达情况和预后价值。方法利用GEPIA在线分析IGFBP家族在肝癌中的基因表达,Kaplan-Meier生存曲线分析IGFBP与预后关系,采用cBioPortal for Cancer Genomics分析肝癌患者中IGFBP基因改变情况。采用GeneMANIA构建IGFBP相关基因作用网络,Metascape数据库基因网络进行基因本体(GO)富集分析。结果GEPIA在线分析显示肝癌IGFBP3 mRNA相对表达量明显低于正常肝组织(P<0.05)。IGFBP3表达与肿瘤病理分期有关(F=5.52,P<0.05)。Kaplan-Meier生存分析显示,IGFBP3和IGFBP4 mRNA表达水平与不良预后密切相关(HR=1.50,0.43;P<0.05)。cBioPortal分析显示肝癌中IGFBP发生基因改变,包括突变、融合、扩增、深缺失和多重改变,其中突变、扩增和深缺失是最常见改变。IGFBPs遗传改变0~1%。GeneMANIA分析确定了20个与IGFBPs密切相关的基因,GO富集分析发现IGFBP主要富集在与生长及细胞运动相关的信号通路中。结论基于生物信息学研究发现IGFBP3在肝癌患者组织中表达异常,且与患者预后相关,IGFBP3可能作为肝癌预后生物标志物和治疗潜在靶点。Objective To explore the expression level and prognostic value of insulin-like growth factor binding protein(IGFBP)family members in hepatocellular carcinoma(HCC)by bioinformatics analysis.Methods The expression levels of IGFBP family members in HCC were analyzed by GEPIA online analysis.The relationship between IGFBP and clinical prognosis was assessed by Kaplan-Meier survival curve.The changes of IGFBP genes in HCC patients were observed by cBioPortal for Cancer Genomics.IGFBP-related gene network was constructed by GeneMANIA.Gene ontology(GO)enrichment analysis was performed by Metascape database.Results GEPIA online analysis showed that the relative expression of IGFBP3 mRNA in HCC was significantly lower than that in normal liver tissues(P<0.05).The expression of IGFBP3 was significantly correlated with the pathological stage of HCC(F=5.52,P<0.05).Kaplan-Meier survival analysis demonstrated that the expression levels of IGFBP3 and IGFBP4 mRNA were significantly associated with poor prognosis(HR=1.50,0.43;P<0.05).cBioPortal analysis revealed that genetic changes of IGFBP in HCC including mutation,fusion,amplification,deep deletion and multiple changes,among which mutation,amplification and deep deletion were the most common changes.The genetic changes of IGFBPs were ranged from 0 to 1%.GeneMANIA analysis identified 20 genes were closely correlated with IGFBPs.GO enrichment analysis found that IGFBP was mainly expressed in the signaling pathways related to growth and cell movement.Conclusions Bioinformaticsbased study demonstrates that IGFBP3 is abnormally expressed in HCC tissues,which is associated with clinical prognosis of HCC patients.IGFBP3 might serve as a biomarker for clinical prognosis and a potential therapeutic target in HCC patients.

关 键 词：癌 肝细胞 胰岛素样生长因子结合蛋白质类 预后 计算生物学 

分 类 号：R735.7[医药卫生—肿瘤]