生物信息学分析CETP基因在肝癌中表达及其对预后和免疫的影响

Bioinformatics analysis of CETP genes expression in primary liver cancer and its effects on prognosis and immunity

目的:探讨胆固醇酯转移蛋白(CETP)在原发性肝癌(肝癌)中表达及其对预后和免疫的影响。方法:下载GEO数据集GSE101685、GSE45267、GSE62232,以及ImmPort数据库人类免疫相关基因(IRGs),联合筛选差异表达的下调基因并选择未研究过的基因CETP。使用UALCAN和Kaplan-Meier Plotter数据库分别分析CETP在肝癌中的表达和其与肝癌患者预后的关系。LinkedOmics数据库进行基因本体(GO)分析和KEGG通路基因富集分析。Timer数据库及TISIDB数据库分析CETP与肝癌免疫细胞浸润、免疫调节剂的相关性。结果:3个肝癌数据集及ImmPort数据库筛选出共有的16个差异基因,从中选择下调的关键基因CETP。UALCAN数据库显示,与正常组织相比,CETP基因在肝癌组织中表达水平降低(P<0.05);CETP表达与美国癌症联合委员会(AJCC)分期、淋巴结转移密切相关(P<0.05)。Kaplan-Meier Plotter数据库分析显示,CETP基因低表达患者中位生存时间37.8个月,明显短于高表达患者的61.7个月(HR=0.66,P<0.05)。GO分析显示,CETP相关基因主要参与免疫反应、白细胞粘附、细胞死亡、细胞趋化等活动;KEGG通路分析显示,CETP基因在NK细胞介导的细胞毒性、细胞因子-细胞因子受体相互作用、氧化磷酸化、Th1和Th2细胞分化等通路中富集。TIMER数据库及TISIDB数据库表明CETP与肝癌中树突状细胞、CD8+T细胞免疫细胞浸润水平及免疫调节剂相关。结论:在线数据库分析表明,CETP基因在肝癌中表达下调,CETP低表达与患者临床特征和不良预后相关,CETP表达的改变可影响免疫应答,从而可能影响患者预后。

Objective To investigate the expression of cholesteryl ester transfer protein(CETP)in primary liver cancer(PLC)and evaluate its effect on prognosis and immunity.Methods The immune-related genes(IRGs)were downloaded from the Gene Expression Omnibus(GEO)datasets including GSE101685,GSE45267 and GSE62232 and ImmPort database.The down-regulated differentially-expressed genes(DEGs)were screened and the unstudied CETP was selected.The expression of CETP in PLC and its association with prognosis of PLC patients were analyzed using UALCAN and Kaplan-Meier Plotter databases,respectively.LinkedOmics database was employed for gene ontology(GO)analysis and KEGG pathway enrichment analysis.Timer and TISIDB databases were adopted to analyze the correlation between CETP and immune cell infiltration and immunomodulators of PLC.Results 16 DEGs were screened from 3 liver cancer datasets and ImmPort database,and the down-regulated key gene of CETP was selected.According to the UALCAN database,the expression level of CETP genes in PLC tissues was lower than that in normal tissues(P<0.05).The expression level of CETP genes was intimately correlated with the American Joint Committee on Cancer(AJCC)staging and lymph node metastasis(P<0.05).Kaplan-Meier Plotter database analysis showed that the median survival of patients with low expression of CETP genes was 37.8 months,significantly shorter than 61.7 months of that with high expression of CETP genes(HR=0.66,P<0.05).GO analysis revealed that CETP-related genes were mainly involved in immune response,leukocyte adhesion,cell death and cell chemotaxis,etc.KEGG pathway analysis showed that CETP gene was enriched in NK cell-mediated cytotoxicity,cytokine-cytokine receptor interaction,oxidative phosphorylation,Th1 and Th2 cell differentiation and other signaling pathways.TIMER and TISIDB databases showed that CETP was associated with the infiltration levels of dendritic cells and CD8+T cells,and immunomodulators in PLC.Conclusions Online database analysis indicates that the expression level of CETP genes is down-regulated in PLC.Low expression of CETP genes is correlated with clinical characteristics and poor prognosis of patients.The changes of CETP genes expression can affect immune response,thereby probably affecting clinical prognosis of PLC patients.