APEX家族在肝细胞癌中的作用及其作为生物标志物的分析研究  

Role of the APEX family in hepatocellular carcinoma and its potential as a biomarker

作　　者：唐希贤 赵楠 曹德东[1] TANG Xixian;ZHAO Nan;CAO Dedong(Cancer Center,Renmin Hospital of Wuhan University,Wuhan,Hubei Province,430061,China)

机构地区：[1]武汉大学人民医院肿瘤中心,武汉430061

出　　处：《陆军军医大学学报》2024年第22期2517-2528,共12页Journal of Army Medical University

基　　金：国家自然科学基金青年科学基金(81700208)。

摘　　要：目的分析APEX家族基因与蛋白在肝细胞癌(hepatocellular carcinoma,HCC)中的作用。方法本研究利用公开数据库(TCGA和TNM plot)收集HCC和正常肝组织的表达数据,通过差异表达分析、蛋白质-蛋白质相互作用网络(protein-protein interactions networks,PPI)建构和基因集富集分析(gene set enrichment analysis,GSEA)探讨APEX家族(APEX1和APEX2)在HCC中的表达模式、功能网络和潜在的生物学通路。采用ROC曲线分析评估APEX家族成员作为HCC诊断标志物的潜力,并通过生存分析探讨其与HCC患者预后的相关性。通过RT-qPCR和Western blot检测肝细胞与HCC细胞中APEX1、APEX2 mRNA和蛋白的表达水平,通过转染分别沉默HCC细胞中APEX1、APEX2,通过CCK-8、EdU、划痕愈合实验和Transwell实验检测APEX1、APEX2对HCC细胞的影响。结果APEX1和APEX2在HCC样本中的表达水平显著高于正常肝组织(P<0.01)。根据公共数据库ROC曲线分析结果显示,APEX1和APEX2预测HCC的AUC值分别为0.922和0.917。PPI网络分析揭示APEX家族成员通过多种信号通路调控细胞周期。生存分析表明,与低表达相比,高表达APEX1、APEX2的HCC患者的整体生存期显著缩短(P<0.05),APEX1与APEX2与Ki-67和TP53传统肿瘤生存预后因子具有高相关性(P<0.001)。肝癌细胞中APEX1、APEX2 mRNA和蛋白的水平显著高于正常肝细胞(P<0.05)。沉默APEX1、APEX2后,HCC细胞的增殖、迁移和侵袭能力均显著降低(P<0.05)。结论APEX1和APEX2可作为HCC诊断和预后评估的潜在生物标志物,APEX1和APEX2参与HCC增殖和转移的调控为HCC的早期诊断和个性化治疗提供了新的策略和靶点。Objective To analyze the role of APEX family in hepatocellular carcinoma(HCC).Methods After expression data of HCC and normal liver tissues from public databases(TCGA and TNM plot)were collected,the expression patterns,functional networks,and potential biological pathways of the APEX family in HCC were investigated through differential expression analysis,construction of protein-protein interaction networks(PPI),and Gene Set Enrichment Analysis(GSEA).Receiver operating characteristic(ROC)curve analysis was used to assess the potential of APEX family members as diagnostic markers for HCC,and their correlation with HCC prognosis was anlyzed through survival analysis.RT-qPCR and Western blotting we performed to detect the expression of APEX1 and APEX2 at mRNA and protein levels in liver cells and HCC cells.The effect of silencing APEX1 and APEX2 in HCC cells were determined through CCK-8 assay,EdU assay,scratch healing test,and Transwell assay.Results The expression levels of the 2 members of the APEX family,APEX1 and APEX2,were significantly higher in the HCC samples than the normal liver tissues(P<0.01).The results of ROC curve analysis on public databases showed that the AUC value of APEX1 and APEX2 in predicting HCC was 0.922 and 0.917,respectively.PPI network analysis revealed that APEX family members regulated cell cycle through various signaling pathways.Survival analysis indicated that HCC patients with high expression levels of APEX1 and APEX2 had significantly shorter overall survival than those with low levels(P<0.05),and APEX1 and APEX2 were highly correlated with traditional tumor survival prognostic factors Ki-67 and TP53(P<0.001).The mRNA and protein levels of APEX1 and APEX2 were significantly higher in the liver cancer cells than the normal liver cells(P<0.05).In addition,silencing APEX1 and APEX2 resulted in notably reduced proliferation,migration,and invasion abilities of HCC cells(P<0.05).Conclusion APEX1 and APEX2 can serve as potential biomarkers for HCC diagnosis and prognosis assessment,and t

关 键 词：肝细胞癌 APEX家族 诊断标志物 治疗靶点 生物信息学分析 

分 类 号：R318.04[医药卫生—生物医学工程] R730.23[医药卫生—基础医学] R735.7