机构地区:[1]上海交通大学医学院附属仁济医院检验科,上海200127 [2]中南大学湘雅医学院检验医学系,湖南长沙410013 [3]中南大学湘雅医院检验科,湖南长沙410008
出 处:《中国肝脏病杂志(电子版)》2024年第3期22-31,共10页Chinese Journal of Liver Diseases:Electronic Version
基 金:湖南省自然科学基金资助项目(2021JJ41023)。
摘 要:目的采用生物信息学方法分析泛素化连接酶TRIM56在人肝细胞癌(hepatocellular carcinoma,HCC)中的表达及其与预后和免疫浸润的关系。方法采用UALCAN和TIMER数据库分析TRIM56在不同肿瘤中的表达。采用UALCAN、TIMER、GEPIA和Human Protein Atlas数据库分析TRIM56在人HCC中的表达。采用Kaplan-Meier Plotter数据库分析不同TRIM56 mRNA表达水平HCC患者的生存情况。采用TIMER数据库和GEPIA数据库对TRIM56的表达与肿瘤纯度及免疫浸润水平的相关性进行分析。采用GeneMANIA数据库筛选与TRIM56相互作用的基因,并使用DAVID数据库对其进行富集分析。采用STRING数据库筛选与TRIM56相互作用的蛋白质,并使用UbiBrowser数据库分析TRIM56可能的泛素化底物。结果GEPIA数据库和UALCAN数据库分析均表明TRIM56在人HCC组织中的表达水平升高,其表达水平与肿瘤纯度和免疫细胞的浸润水平有关(P均<0.05)。对于亚洲患者,TRIM56 mRNA高表达者的5年总生存率和无复发生存率均显著高于TRIM56 mRNA低表达者(HR=0.43,Log-rank P=0.029;HR=0.45,Log-rank P=0.016);而对于欧美患者,两者差异均无统计学意义(HR=1.37,Log-rank P=0.22;HR=0.70,Log-rank P=0.14)。基因互作及富集分析表明,TRIM56可能参与核苷酸修复和线粒体自噬等过程,TP53是评分最高的预测泛素化底物(0.867分),可能与TRIM56参与介导人HCC发生发展的机制相关。结论TRIM56可能与HCC的发生发展和免疫浸润有关,其高表达可能提高亚洲HCC患者的生存率,为进一步研究TRIM56在HCC中的潜在作用机制奠定了基础。Objective To analyze the expression of ubiquitinated ligase TRIM56 in human hepatocellular carcinoma(HCC)and its relationship with prognosis and immune infiltration by bioinformatics methods.Methods The expression of TRIM56 in various tumors were analyzed by UALCAN and TIMER databases.The expression of TRIM56 in human HCC tissues were analyzed by UALCAN,TIMER,GEPIA and Human Protein Atlas databases.Kaplan Meier Plotter database was used to analyze the survival status of HCC patients with different TRIM56 expression levels.TIMER database and GEPIA database were used to analyze the correlation between the expression of TRIM56 and tumor purity and immune infiltration levels.GeneMANIA database was used to screen genes related with TRIM56 and DAVID database was used to conduct enrichment analysis on them.STRING database was used to screen proteins related with TRIM56 and UbiBrowser database was used to analyze potential ubiquitination substrates of TRIM56.Results Both GEPIA and UALCAN database analyses indicated that the expression level of TRIM56 increased in human HCC tissues,and its expression levels were related to tumor purity and immune cell infiltration levels(all P<0.05).For Asian patients,the five-year overall survival rate and recurrence free survival rate of TRIM56 mRNA high expression patients were significantly higher than those of TRIM56 mRNA low expression patients(HR=0.43,Log-rank P=0.029;HR=0.45,Log-rank P=0.016).For European and American patients,there were no statistically significant differences in five-year overall survival rate or recurrence free survival rate(HR=1.37,Log-rank P=0.22;HR=0.70,Log-rank P=0.14).Gene interaction and enrichment analysis indicated that TRIM56 may be involved in processes such as nucleotide repair and mitochondrial autophagy.TP53 was the highest rated predicted ubiquitination substrate(0.867 points),which may be related to TRIM56’s involvement in mediating the occurrence and development of human HCC.Conclusions TRIM56 may be related to the occurrence,development and i
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