细胞分裂后期促进复合亚基2在肝细胞癌组织中的表达及临床意义  

Expression of anaphase promoting complex subunit 2 in hepatocellular carcinoma and its clinical significance

作　　者：吴薇紫[1] 覃凯 秦铭坚 陈吉添[1] 莫伟嘉[2] 罗婕[3] Wu Weizi;Qin Kai;Qin Mingjian;Chen Jitian;Mo Weijia;Luo Jie(Department of Pathology,Lingshan People's Hospital,Qinzhou,Guangxi 535400,China;Department of Pathology,The First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi 530021,China;Department of Medical Oncology,The Second Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi 530001,China)

机构地区：[1]广西钦州市灵山县人民医院病理科,广西钦州535400 [2]广西医科大学第一附属医院病理科,广西南宁530021 [3]广西医科大学第二附属医院肿瘤内科,广西南宁530001

出　　处：《齐齐哈尔医学院学报》2024年第20期1901-1913,共13页Journal of Qiqihar Medical University

基　　金：广西壮族自治区卫生健康委员会科研课题(Z20190523)。

摘　　要：目的探究细胞分裂后期促进复合亚基2(Anaphase promoting complex subunit 2,ANAPC2)在肝细胞癌(Hepatocellular carcinoma,HCC)组织中的表达和其相关潜在功能机制。方法使用组织芯片免疫组化评估HCC及正常肝脏组织中ANAPC2蛋白表达的水平,并基于基因芯片和RNA测序的高通量数据库,计算ANAPC2 mRNA在HCC中的表达水平。利用单细胞测序技术进一步验证ANAPC2在HCC细胞层面的表达水平,并运用CRISPR敲除探究ANAPC2基因对HCC细胞生长的影响。使用Pearson相关分析筛选出ANAPC2的共表达基因,对该基因集进行功能富集分析。结果与正常肝组织相比,HCC组织中ANAPC2蛋白的表达出现了上调趋势。高通量数据集检索共纳入3861个HCC和3136个非癌肝组织样本,发现ANAPC2 mRNA在HCC组织中高表达(SMD=0.18,95%CI:0.04~0.32,P<0.05),sROC曲线下面积为0.67(95%CI:0.63~0.71)。在HCC单细胞水平也证实了ANAPC2的表达上调,ANAPC2基因的敲除可显著抑制HCC细胞的生长。ANAPC2共表达基因显著富集的信号通路包括细胞周期和有丝分裂等。结论HCC中,ANAPC2在转录及翻译阶段均表达上调,发挥了一定的促癌功能。Objective To investigate the expression and potential functional mechanisms of Anaphase Promoting Complex Subunit 2(ANAPC2)in hepatocellular carcinoma(HCC)tissues.Methods Tissue microarray and immunohistochemical technology were utilized to assess ANAPC2 protein expression levels in HCC and normal liver tissues.High-throughput databases from gene chips and RNA sequencing were used to examine ANAPC2 mRNA expression levels in HCC.Single-cell RNA sequencing technology was further employed to validate ANAPC2 expression at the cellular level in HCC,and CRISPR knockout was conducted to investigate the impact of ANAPC2 on the cell growth of HCC.Pearson correlation analysis was used to identify co-expressed genes with ANAPC2,followed by functional enrichment analysis of the gene set.Results ANAPC2 protein expression showed an up-regulation trend in HCC tissues compared to normal liver tissues.A total of 3861 HCC and 3136 non-HCC liver tissue samples were included in the high-throughput datasets,revealing significantly higher ANAPC2 mRNA expression in HCC tissues(SMD=0.18,95%CI:0.04~0.32,P<0.05),and the area under the sROC curve was 0.67(95%CI:0.63~0.71).At the single-cell level in HCC,up-regulation of ANAPC2 expression was confirmed,and knockout of the ANAPC2 gene significantly inhibited the cell growth of HCC.The enriched signaling pathways among ANAPC2 co-expressed genes included the cell cycle and mitosis.Conclusions In HCC,ANAPC2 is up-regulated at both the transcriptional and translational levels,exerting a pro-oncogenic function.

关 键 词：肝细胞癌 细胞分裂后期促进复合亚基2(ANAPC2) 基因芯片 RNA测序 单细胞测序 

分 类 号：R735[医药卫生—肿瘤]