TRIM31与慢性肝病的孟德尔随机化及生物信息学分析  

Mendelian randomization and bioinformatics analysis of TRIM31 with chronic liver disease

作　　者：尤君怡[1] 梁国强[2] 宋秀道 YOU Junyi;LIANG Guoqiang;SONG Xiudao(Surgical Department of Traditional Chinese Medicine,Suzhou Hospital of Traditional Chinese Medicine affiliated to Nanjing University of Chinese Medicine,Suzhou 215009,Jiangsu Province,China;Central laboratory,Suzhou Hospital of Traditional Chinese Medicine affiliated to Nanjing University of Chinese Medicine,Suzhou 215009,Jiangsu Province,China;Centre for Translation of Traditional Chinese Medicine Science and Technology,Suzhou Hospital of Traditional Chinese Medicine Hospital affiliated to Nanjing University of Chinese Medicine,Suzhou 215009,Jiangsu Province,China)

机构地区：[1]南京中医药大学附属苏州市中医医院中医外科,江苏苏州215009 [2]南京中医药大学附属苏州市中医医院中心实验室,江苏苏州215009 [3]南京中医药大学附属苏州市中医医院中医药科技转化中心,江苏苏州215009

出　　处：《医学新知》2025年第3期303-311,I0008,I0009,共11页New Medicine

基　　金：国家自然科学基金面上项目(82374546);苏州市姑苏卫生人才计划人才科研项目(GSWS2021048);江苏省中医药科技发展计划项目(MS2024079);江苏省卫生健康委医学科研项目(M2024049);苏州市科技发展计划(基础研究-医学应用基础研究)项目(SKY2023218)。

摘　　要：目的使用两样本孟德尔随机化(Mendelian randomization,MR)分析评估肝脏TRIM31表达水平与慢性肝病的因果关系,以及生物信息学方法分析TRIM31在肝细胞癌(hepatocellular carcinoma,HCC)中的作用。方法利用FinnGen R10数据库中非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)、非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)、肝纤维化、肝硬化、HCC的遗传数据,以及GTEx Portal肝组织cis-eQTL数据中与TRIM31表达显著相关的单核苷酸多态性作为工具变量,采用逆方差加权法作为主要方法进行MR分析。使用TCGA分析TRIM31在HCC中的表达,并利用CIBERSORT算法分析TRIM31表达与免疫细胞浸润的相关性,ROC曲线评估诊断准确性。使用TCGA数据库进行高和低TRIM31表达组之间的差异基因表达分析,并进行GO富集、KEGG通路富集和基因集富集分析(gene set enrichment analysis,GSEA)。结果M R分析结果显示,肝脏TRIM31表达与NAFLD[OR=0.98,95%CI(0.91,1.05),P=0.515]、NASH[OR=0.98,95%CI(0.74,1.29),P=0.868]、肝纤维化[OR=1.35,95%CI(0.84,2.17),P=0.218]、肝硬化[OR=1.06,95%CI(0.95,1.17)P=0.292]均不存在显著关联;与HCC[OR=1.26,95%CI(1.07,1.49),P=0.007]存在显著关联。TCGA数据分析显示,HCC组织中TRIM31 mRNA水平显著增加(P<0.001)。ROC分析显示,TRIM31在HCC诊断中的曲线下面积为0.794[95%CI(0.738,0.851)]。高TRIM31表达与免疫评分增加以及活化记忆CD4+T细胞、滤泡辅助性T细胞、调节性T细胞的比例增加相关,而与单核细胞和M2型巨噬细胞比例减少相关。GSEA分析显示,TRIM31高表达的HCC样本中显著富集与肿瘤恶性进展密切相关的信号通路,包括生物氧化信号通路(FDR<0.05,NES=2.329)、钙信号传导通路(FDR<0.05,NES=2.283)等。结论肝脏TRIM31表达上调可能增加HCC患病风险,可能与肿瘤免疫微环境的调控有关,为HCC发病机制的研究提供理论依据。Objective Using two-sample Mendelian randomization(MR)to explore the causal relationship between the expression level of tripartite motif 31(TRIM31)in chronic liver disease,and using bioinformatics methods to analyze the role of TRIM31 in hepatocellular carcinoma(HCC).Methods The genetic data for non-alcoholic fatty liver disease(NAFLD),non-alcoholic steatohepatitis(NASH),liver fibrosis,cirrhosis,and HCC from the FinnGen R10,as well as the instrumental variables of single nucleotide polymorphisms(SNPs)significantly associated with TRIM31 expression in the cis eQTL data of GTEx Portal liver tissue were used for MR analysis,with the inverse-variance weighting as the main analysis method.The expression level of TRIM31 in HCC was analyzed using TCGA data,and the correlation between TRIM31 expression and immune cell infiltration was analyzed using the CIBERSORT algorithm.The diagnostic accuracy was evaluated by ROC curves.Differential gene expression analysis between high and low TRIM31 expression groups was performed using the TCGA database,and Gene Ontology(GO)enrichment,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and Gene Set Enrichment Analysis(GSEA)were conducted.Results The MR analysis results showed that the expression of TRIM31 in the liver was not significantly associated with NAFLD[OR=0.98,95%CI(0.91,1.05),P=0.515],NASH[OR=0.98,95%CI(0.74,1.29),P=0.868],liver fibrosis[OR=1.35,95%CI(0.84,2.17),P=0.218],and cirrhosis[OR=1.06,95%CI(0.95,1.17),P=0.292],but was significant associated with HCC[OR=1.26,95%CI(1.07,1.49),P=0.007].TCGA data analysis showed that compared with normal liver tissue,TRIM31 mRNA levels were significantly increased in HCC(P<0.001).ROC analysis showed that the area under the curve for TRIM31 in HCC diagnosis was 0.794[95%CI(0.738,0.851)].High TRIM31 expression was associated with increased immune scores and proportions of activated memory CD4+T cells,follicular helper T cells,regulatory T cells,while being inversely related to monocytes and M2 macrophages.GSEA analysis rev

关 键 词：孟德尔随机化 三重基序蛋白31 慢性肝病 肝细胞癌 生物信息学 

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