IGFBP3基因的异常表达与肝细胞癌的预后关系  

Abnormal Expression of IGFBP3 Gene and Prognosis of Hepatocellular Carcinoma

作　　者：夏磊 阮梅 黄倩 方坚 XIA Lei;RUAN Mei;HUANG Qian;FANG Jian(Department of Hepatobiliary Internal Medicine,the Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou Fujian 350012,China)

机构地区：[1]福建中医药大学附属第三人民医院肝胆科,福建福州350012

出　　处：《中国卫生标准管理》2024年第16期135-141,共7页China Health Standard Management

基　　金：福建省中青年教师教育科研项目(JAT210167)。

摘　　要：目的探讨胰岛素样生长因子结合蛋白3(insulin-like growth factor binding protein 3,IGFBP3)在肝细胞癌中的临床意义及其在HepG2肝癌细胞中的作用机制。方法本研究通过加权基因共表达网络分析(weighted correlation network analysis,WGCNA)和差异表达基因分析,使用癌症基因组图谱(the cancer genome atlas,TCGA)数据库和基因表达汇编(gene expression omnibus,GEO)数据库中的GSE54236数据集,分析IGFBP3的功能富集及其与肝癌临床病理特征的关系。利用慢病毒转染技术构建过表达IGFBP3的HepG2细胞,并通过划痕愈合实验和细胞计数试剂-8(cell counting kit-8,CCK-8)增殖实验测试细胞的迁移与增殖能力。结果从TCGA和GSE54236中识别出54个共同差异基因,基因本体(gene ontology,GO)分析显示主要富集在上皮细胞增殖、急性炎症反应及补体激活等生物过程;细胞组成主要在胶原蛋白和胞质囊腔;分子功能在碳水化合物和肽类结合。京都基因与基因组百科全书(kyoto encyclopedia of genes andgenomes,KEGG)分析显示信号通路涉及神经活性配体受体相互作用等。IGFBP3是与肝癌总生存期显著相关的中枢基因,且在肝癌组织中表达低,与肿瘤分期和淋巴结转移相关。过表达IGFBP3的HepG2细胞显示增强的迁移和增殖能力。结论IGFBP3在肝细胞癌中表达低且与患者总生存期预后相关,其过表达促进HepG2细胞的迁移和增殖。Objective To investigate the clinical significance of insulin-like growth factor binding protein 3(IGFBP3)in hepatocellular carcinoma and its mechanism of action in HepG2 hepatocellular carcinoma cells.Methods In this study,weighted correlation network analysis(WGCNA)and differential expression gene analysis were used,the functional enrichment of IGFBP3 and its relationship with the clinicopathological features of hepatocellular carcinoma were analyzed using the GSE54236 dataset in the cancer genome atlas(TCGA)and gene expression omnibus(GEO)databases.HepG2 cells with IGFPB3 overexpression were constructed by lentivirus transfection technique.The migration and proliferation capacity of HepG2 were determined by scratch healing assay and cell counting kit-8(CCK-8)proliferation assay.Results A total of 54 common differentially expressed genes were identified from TCGA and GSE54236.Gene ontology(GO)analysis showed significant enrichment in biological processes such as epithelial cell proliferation,acute inflammatory response,and complement activation,cellular components mainly included collagen and cytoplasmic vesicles,molecular functions involved carbohydrate and peptide binding.Kyoto encyclopedia of genes andgenomes(KEGG)analysis indicated pathways involved in neuroactive ligand-receptor interaction,among others.IGFBP3 was a central gene significantly correlated with overall survival in liver cancer,expressed at low levels in liver cancer tissues,and associated with tumor staging and lymph node metastasis.HepG2 cells overexpressing IGFBP3 exhibited enhanced migration and proliferation capabilities.Conclusion IGFBP3 is low expressed in hepatocellular carcinoma and is associated with overall survival of patients with hepatocellular carcinoma.Overexpression of IGFBP3 promotes migration and proliferation of HepG2 hepatoma cells.

关 键 词：肝细胞癌 预后 胰岛样生长因子结合蛋白3 基因 增殖 迁移 

分 类 号：R735[医药卫生—肿瘤]