Mendelian randomization and bioinformatics analysis of TRIM31 with chronic liver disease

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