Comprehensive Analysis of the Prognostic Values of the TRIM Family in Hepatocellular Carcinoma

Abstract

BackgroundAccumulating studies have demonstrated the abnormal expressions and prognostic values of certain members of the tripartite motif (TRIM) family in diverse cancers. However, comprehensive prognostic values of the TRIM family in hepatocellular carcinoma (HCC) are yet to be clearly defined.MethodsThe prognostic values of the TRIM family were evaluated by survival analysis and univariate Cox regression analysis based on gene expression data and clinical data of HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The expression profiles, protein–protein interaction among the TRIM family, prediction of transcription factors (TFs) or miRNAs, genetic alterations, correlations with the hallmarks of cancer and immune infiltrates, and pathway enrichment analysis were explored by multiple public databases. Further, a TRIM family gene-based signature for predicting overall survival (OS) in HCC was built by using the least absolute shrinkage and selection operator (LASSO) regression. TCGA–Liver Hepatocellular Carcinoma (LIHC) cohort was used as the training set, and GSE76427 was used for external validation. Time-dependent receiver operating characteristic (ROC) and survival analysis were used to estimate the signature. Finally, a nomogram combining the TRIM family risk score and clinical parameters was established.ResultsHigh expressions of TRIM family members including TRIM3, TRIM5, MID1, TRIM21, TRIM27, TRIM32, TRIM44, TRIM47, and TRIM72 were significantly associated with HCC patients’ poor OS. A novel TRIM family gene-based signature (including TRIM5, MID1, TRIM21, TRIM32, TRIM44, and TRIM47) was built for OS prediction in HCC. ROC curves suggested the signature’s good performance in OS prediction. HCC patients in the high-risk group had poorer OS than the low-risk patients based on the signature. A nomogram integrating the TRIM family risk score, age, and TNM stage was established. The ROC curves suggested that the signature presented better discrimination than the similar model without the TRIM family risk score.ConclusionOur study identified the potential application values of the TRIM family for outcome prediction in HCC.

TRIM proteins in hepatocellular carcinoma

“…Another study built a TRIM gene-based signature (including TRIM5, MID1(TRIM18), TRIM21, TRIM32, TRIM44, and TRIM47), which shows decent efficiency in predicting OS [HR: 6.630 (3.030–14.504), p < 0.001] in TCGA and GSE76427. A nomogram based on risk score, age, and TNM stage also showed better discrimination in predicting OS [ 65 ].…”

TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability

“…Targeting cellular metabolism has great potential to improve responsiveness to immunotherapies [ 46 ]. Furthermore, TRIM21 was reported to be highly expressed in immune cells, such as B cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells, through the Tumor Immune Estimation Resource (TIMER) database [ 47 ]. Whether TRIM21 is involved in the metabolic phenotype changes of immune cells and the crosstalk between metabolic activities mediated by TRIM21 still needs to be explored.…”

TRIM21 aggravates cardiac injury after myocardial infarction by promoting M1 macrophage polarization

“…Tripartite motif-containing proteins (TRIMs) are a large family of E3 ubiquitin ligases containing three highly conserved domains, namely a RING (Really Interesting New Gene) finger, one or two B -box domains, and a coiled-coil domain ( 31 ). TRIMs family contains more than 70 members and participates in multiple cellular cascades, including the immunity response, tumor progression, and autophagy ( 14 , 32 – 34 ). Recently, the effects of TRIMs on myocardial ischemia were explored.…”