酪氨酸氨基转移酶基因在肝细胞癌中诊疗价值及其底物酪氨酸的孟德尔随机化研究  

Prognostic value of tyrosine aminotransferase in hepatocellular carcinoma and Mendelian randomization study of its substrate-tyrosine

作　　者：李雅菲 隋丽娜 宋承桂 郭添福 刘志平 LI Ya-fei;SUI Li-na;SONG Cheng-gui;GUO Tian-fu;LIU Zhi-ping(School of Basic Medicine,Gannan Medical University;The First Clinical Medical School of Gannan Medical University,Ganzhou,Jiangxi 341000)

机构地区：[1]赣南医科大学基础医学院 [2]赣南医科大学第一临床医学院,江西赣州341000

出　　处：《赣南医科大学学报》2025年第2期107-116,共10页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：国家自然科学基金项目(31960163);江西省自然科学基金项目(20212BAB206003)。

摘　　要：目的:利用GEO、TCGA和STRING数据集研究酪氨酸氨基转移酶基因(Tyrosine aminotransferase gene,TAT)在肝细胞癌(Hepatocellular carcinoma,HCC)中的临床价值和潜在功能。方法:使用GEO、TCGA、STRING、LinkedOmics、TargetScan、miRDB、miRWalk和GEPIA数据库分析HCC患者TAT基因表达与预后、临床分期和免疫细胞浸润之间的相关性,并获得了与TAT直接相互作用的分子。免疫组织化学(Immunohistochemistry,IHC)染色证实TAT在HCC中的表达情况。GO和KEGG富集分析TAT在HCC中的潜在作用。通过2个样本的孟德尔随机化分析TAT底物(酪氨酸)与HCC之间的因果关系。结果:IHC证实TAT在HCC样品中显著低表达。共表达和差异分析得到11个共表达基因,这些基因主要参与氨基酸的代谢。其中PCK1、SDS、BHMT、CYP2A6和CTH可与TAT直接相互作用。生存分析显示,TAT、CTH或BHMT低表达患者的总生存率显著降低。发现miR-212对TAT的表达有显著影响。免疫细胞浸润的分析揭示了10种免疫细胞类型,在高和低TAT表达组之间有显著差异。双样本孟德尔分析发现,TAT可能不是直接通过调节酪氨酸水平来抑制HCC。结论:TAT可作为HCC的诊断标志物,为HCC的诊断和治疗提供新的理论依据。Objective:To utilize GEO,TCGA and STRING datasets to investigate the clinical value and potential function of tyrosine aminotransferase gene(TAT)in hepatocellular carcinoma(HCC).Methods:The correlation between TAT gene expression and prognosis,clinical stage and immune cell infiltration in HCC patients was analyzed using databases such as GEO,TCGA and STRING and online tools such as GEPIA,and molecules that directly interact with TAT were obtained.Immunohistochemistry(IHC)staining confirmed the expression of TAT in HCC.GO and KEGG enrichment was performed to analyze the potential role of TAT in HCC.The causality between TAT substrate(tyrosine)and HCC was analyzed by Mendelian randomization of two samples.Results:IHC confirmed that TAT was significantly under-expressed in HCC samples.Co-expression and differential analysis yielded 11 co-expressed genes,which are mainly involved in amino acid metabolism.Among them,PCK1,SDS,BHMT,CYP2A6 and CTH could directly interact with TAT.Survival analysis showed that patients with low expression of TAT,CTH or BHMT had significantly lower overall survival.It was found that miR-212 had a significant effect on TAT expression.Analysis of immune cell infiltration revealed 10 immune cell types with significant differences between high and low TAT expression groups.Two-sample Mendelian analysis revealed that TAT may not inhibit HCC directly by regulating tyrosine levels.Conclusion:TAT can be used as a diagnostic marker for HCC,providing a new theoretical basis for the diagnosis and treatment of HCC.

关 键 词：酪氨酸氨基转移酶 肝细胞癌 孟德尔随机化 

分 类 号：R735.7[医药卫生—肿瘤]