基于GEO数据库的肝癌相关基因的筛选及验证  

Screening and Validation of Hepatocellular Carcinoma Related Genes Based on GEO Database

作　　者：仇林 黄健 Qiu Lin;Huang Jian(Key Laboratory of Systems Biomedicine(Ministry of Education),Shanghai Center for Systems Biomedicine,Shanghai Jiao Tong University,Shanghai,200240)

机构地区：[1]上海交通大学系统生物医学研究院,系统生物医学教育部重点实验室,上海200240

出　　处：《基因组学与应用生物学》2021年第2期899-908,共10页Genomics and Applied Biology

基　　金：国家自然科学基金委面上项目基金项目(18Z103010173);上海市科委重点项目(19Z111220022)共同资助。

摘　　要：肝细胞癌(hepatocellular carcinoma,HCC)是中国高发的恶性肿瘤之一,识别肝细胞癌发生发展相关基因,对于深入研究肝癌发病机制和开发诊疗靶点均具有重要意义。本研究利用GEO_(2)R工具从基因表达汇编数据库(Gene Expression Omnibus Database,GEO)筛选5个数据集中共有的差异表达基因作为潜在的肝癌相关基因。利用Metascape网站,对差异表达基因进行功能富集及信号通路分析。结合GEPIA(Gene Expression Profiling Interaction Analysis)网站筛选具有临床意义的基因。利用荧光定量PCR技术验证与肝癌预后相关的差异表达基因,候选肝癌相关基因,为后续的深入研究奠定扎实的基础。结果显示,从5个数据集中共发现94个共有的差异表达基因。文献检索后发现24个基因与肝癌发生发展的关系少见文献报道,属于肝癌中未知功能基因。利用GEPIA分析癌症基因组图谱(the cancer genome atlas,TCGA)中数据后发现,GINS1在肝癌组织中高表达,与肝癌患者生存期呈负相关;CFHR4和DNASE1L3在肝癌组织中显著低表达,与肝癌患者生存期呈正相关。荧光定量PCR技术证实GINS1在81.3%的肝癌组织中呈现高表达,CFHR4和DNASE1L3分别在71.9%和93.8%肝癌组织中低表达。因此,本研究发现GINS1、CFHR4和DNASE1L3在肝癌组织中显著差异表达,与肝癌患者的预后密切相关,可能作为潜在的判断肝癌患者预后的分子标志物和研发肝癌治疗的潜在靶标。Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in China.Identifying the genes related to the development of HCC is of great significance for the in-depth study of the pathogenesis of HCC and the development of therapeutic targets.The GEO_(2) R tool was used to screen the differentially expressed genes common to five data sets from the Gene Expression Omnibus Database(GEO).Those differentially expressed genes were potential hepatocellular cancer-related genes.Functional enrichment and signal pathway analysis of differentially expressed genes were carried out by Metascape.The Gene Expression Profiling Interaction Analysis(GEPIA)was used to identify gene closely related to clinical significance of HCC patients.Real-time fluorescence quantitative PCR was used to verify the differentially expressed genes related to the prognosis of liver cancer and to identify the candidate genes related to liver cancer,laying a solid foundation for further research.The results showed that a total of 94 differentially expressed genes were shared by the 5 data sets.After literature search,it was found that the relationship between 24 genes and the development of HCC was rarely reported in literature,and they were unknown functional genes in HCC.After analyzing the data in The Cancer Genome Atlas(TCGA)with the GEPIA,it was found that GINS1 was highly expressed in liver cancer tissues and negatively correlated with the survival of liver cancer patients.CFHR4 and DNASE1 L3 were significantly lower expressed in liver cancer tissues and were positively correlated with the survival of liver cancer patients.Real-time fluorescence quantitative PCR confirmed that GINS1 was highly expressed in 81.3%HCC tissues,while CFHR4 and DNASE1 L3 were respectively low expressed in 71.9%and 93.8%HCC tissues.Therefore,it was found that GINS1,CFHR4 and DNASE1 L3 were significantly differential expressed in HCC tissues,which were closely associated to the prognosis of HCC patients,and may be used as potential molecular markers to diagn

关 键 词：肝细胞癌 差异表达基因 分子标志物 

分 类 号：R735.7[医药卫生—肿瘤]