糖酵解相关基因与肝细胞癌患者预后关系的研究  

ASSOCIATION OF GLYCOLYSIS-RELATED GENES WITH THE PROGNOSIS OF PATIENTS WITH HEPATOCELLULAR CARCINOMA

作　　者：解宇威 刘鹏[1] 徐翔宇 高瑞谦 高雨菲 刘奎[1] 李坤[1] 朱呈瞻 曹景玉[1] XIE Yuwei;LIU Peng;XU Xiangyu;GAO Ruiqian;GAO Yufei;LIU Kui;LI Kun;ZHU Chengzhan;CAO Jingyu(Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, China)

机构地区：[1]青岛大学附属医院肝胆胰外科,山东青岛266003

出　　处：《精准医学杂志》2022年第2期141-146,共6页Journal of Precision Medicine

基　　金：山东省高等学校青创科技支撑计划(2020KJL005)。

摘　　要：目的探究肝细胞癌(Hepatocellular carcinoma,HCC)中糖酵解相关基因与肝细胞癌发生发展及预后的关系。方法从癌症基因组图谱(TCGA)数据库下载HCC的RNA表达数据和临床信息。首先采用基因富集分析预测正常组织和肿瘤组织中基因富集的相关通路,筛选HCC中糖酵解相关基因,然后构建糖酵解相关基因的预后模型,获取预后相关糖酵解基因。对基因进行风险评分,利用R语言根据临床特征分组后进行生存分析。使用cBioPortal数据库,分析预后模型中基因的突变情况。最后使用RT-qPCR验证预后模型中基因在HCC的表达。结果基因富集分析显示,正常样本和肿瘤样本的基因显著富集于糖酵解通路。Cox回归分析筛选出了3个与预后相关的糖酵解基因(B3GAT3、NDC1、KIF20A),ROC曲线AUC值显示预后相关的糖酵解基因能预测HCC患者的临床预后,生存分析显示基因高表达组患者的总体生存率比低表达组患者更差(P<0.001)。cBioPortal数据库分析B3GAT3发生扩增、深度缺失和错义突变的概率为1.1%,NDC1发生扩增和错义突变的概率为0.6%,KIF20A发生扩增和错义突变的概率为0.8%。RT-qPCR结果显示B3GAT3、NDC1、KIF20A在HCC组织中均为高表达。结论糖酵解相关基因B3GAT3、NDC1、KIF20A与HCC的预后相关,为后续进一步探究其在HCC中的作用机制提供了依据。Objective To investigate the association of glycolysis-related genes with the development,progression,and prognosis of hepatocellular carcinoma(HCC).Methods The RNA expression data and clinical information of HCC were downloaded from The Cancer Genome Atlas(TCGA)database.Gene Set Enrichment Analysis(GSEA)was used to predict the pathways of gene enrichment in normal tissue and tumor tissue to screen out the glycolysis-related genes in HCC,and then a prognostic model was established based on glycolysis-related genes to obtain the genes associated with prognosis.The risk scores of the genes were determined,and R language was used to perform survival analysis after grouping according to clinical features.The cBioPortal database was used to analyze mutations of the genes in the prognostic model,and finally,RT-qPCR was used to validate the expression of genes in HCC in the prognostic model.Results GSEA analysis suggested that the genes were significantly enriched in the glycolysis pathway in both normal and tumor tissue samples.The Cox regression analysis screened out three glycolysis-rela-ted genes associated with prognosis,i.e.,B3GAT3,NDC1,and KIF20A,and the area under the ROC curve showed that the glycolysis-related genes associated with prognosis could be used to predict the clinical prognosis of HCC patients;survival analysis showed that the patients with high expression of genes had a poorer overall survival rate than those with low expression(P<0.001).The cBioPortal database analysis showed that the probability of amplification,deep deletion,and missense mutation was 1.1%for B3GAT3,the probability of amplification and missense mutation was 0.6%for NDC1,and the probability of amplification and missense mutation was 0.8%for KIF20A.RT-qPCR results showed that B3GAT3,NDC1,and KIF20A were highly expressed in HCC tissue.Conclusion The glycolysis-related genes B3GAT3,NDC1,and KIF20A are associated with the prognosis of HCC,which provides a basis for further exploration of their mechanism of action in HCC.

关 键 词：癌 肝细胞 糖酵解 基因表达调控 肿瘤 预后 基因组学 计算生物学 

分 类 号：R735.7[医药卫生—肿瘤] R394[医药卫生—临床医学]