泛素化连接酶TRIM56在人肝细胞癌中的表达及其与预后和免疫浸润关系的生物信息学分析

作者：黄海芊1 2  王堃3

单位：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

关键词：生物信息学分析 TRIM56 肝细胞癌

分类号：

出版年,卷(期):页码：2024,16(3):22-31

摘要：

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。

Abstract: 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.   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 immune infiltration of HCC, and its high expression may improve the survival rate of Asian HCC patients, which laid 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 immune infiltration of HCC, and its high expression may improve the survival rate of Asian HCC patients, which laid the foundation for further research on the potential mechanism of TRIM56 in HCC.

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