慢性乙型肝炎发展为肝细胞癌过程中血浆游离氨基酸水平的变化及临床意义  

Changes and clinical significance of plasma free amino acid levels in the development of chronic hepatitis B to hepatocellular carcinoma

作　　者：吴静[1] 范志娟[1] 刘树业[1] WU Jing;FAN Zhijuan;LIU Shuye(Department of Clinical Laboratory,the Third Central Hospital of Tianjin,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases,Artificial Cell Engineering Technology Research Center,Tianjin Institute of Hepatobiliary Disease,Tianjin 300170,China)

机构地区：[1]天津市第三中心医院检验科,天津市重症疾病体外生命支持重点实验室,天津市人工细胞工程技术研究中心,天津市肝胆疾病研究所,300170

出　　处：《天津医药》2024年第7期738-743,共6页Tianjin Medical Journal

基　　金：天津市卫生健康科技项目重点学科专项(TJWJ2023XK021)。

摘　　要：目的探究慢性乙型肝炎(CHB)发展为肝硬化(LC)并最终发展为肝细胞癌(HCC)过程中血浆游离氨基酸水平的变化及临床意义。方法对49例CHB患者(CHB组)、43例CHB相关LC患者(LC组)和50例CHB相关HCC患者(HCC组)的血浆样本进行氨基酸谱的分析,比较各组间氨基酸水平的差异。同时采用MetaboAnalyst网站对相关的氨基酸代谢通路进行分析。结果共鉴定出16种表达水平有差异的氨基酸。从CHB发展到LC再到HCC的过程中,血浆胱氨酸、苯丙氨酸和甘氨酸水平逐渐升高,支链氨基酸/芳香族氨基酸逐渐降低;与CHB组和LC组比较,HCC组中的牛磺酸、蛋氨酸、酪氨酸、鸟氨酸、谷氨酸、异亮氨酸和色氨酸水平升高,精氨酸水平降低;与CHB组比较,LC组和HCC组中丝氨酸、丙氨酸、脯氨酸升高,HCC组中缬氨酸水平升高(均P<0.05)。3组的代谢通路分析表明,苯丙氨酸、酪氨酸和色氨酸生物合成,苯丙氨酸代谢,甘氨酸、丝氨酸和苏氨酸代谢,缬氨酸、亮氨酸和异亮氨酸生物合成和牛磺酸代谢等多种代谢途径发生了显著变化。此外,通过构建氨基酸-酶-基因相互作用的网络图,共发现了79个与氨基酸表达相关的代谢酶基因。结论血浆氨基酸水平对肝癌的早期预警和预后具有一定指导意义,可为肝癌的早期预警和治疗提供理论基础和方法依据。Objective To investigate changes and clinical significance in plasma free amino acid levels during the progression from chronic hepatitis B(CHB)to liver cirrhosis(LC)and ultimately to hepatocellular carcinoma(HCC).Methods The plasma samples of 49 CHB patients,43 CHB-related LC patients and 50 CHB-related HCC patients were analyzed using the Hitachi L-8900 amino acid analyzer.The differences in amino acid levels were compared between groups.Simultaneously,the MetaboAnalyst website was used to analyze the relevant amino acid metabolism pathways.Results A total of 16 amino acids with different expression levels were identified.During the development from CHB to HCC,plasma levels of cystine,phenylalanine and glycine gradually increased,while the ratio of branched chain amino acids/aromatic amino acids gradually decreased.Compared with the CHB and the LC groups,levels of taurine,methionine,tyrosine,ornithine,glutamate,isoleucine and tryptophan were significantly increased in the HCC group,while the level of arginine was significantly lower.Compared with the CHB group,levels of serine,alanine and proline were higher in the LC and the HCC groups,while the level of valine was also higher in the HCC group(all P<0.05).The metabolic pathway analysis of three groups showed significant changes in various metabolic pathways,including phenylalanine,tyrosine,tryptophan biosynthesis,phenylalanine metabolism,glycine,serine,threonine metabolism,valine,leucine,isoleucine biosynthesis,and taurine metabolism.In addition,by constructing a network diagram of amino acid enzyme gene interactions,a total of 79 metabolic enzyme genes related to amino acid expression were discovered.Conclusion Plasma levels of amino acids are of certain guiding significance for early warning and prognosis of HCC and can provide a theoretical basis and methodological basis for the diagnosis and treatment of HCC in the future.

关 键 词：乙型肝炎 慢性 肝硬化 肝肿瘤 氨基酸类 

分 类 号：R575.1[医药卫生—消化系统] R575.2[医药卫生—内科学] R735.7[医药卫生—临床医学]