Research Paper Volume 15, Issue 12 pp 5798—5825
Comprehensive analysis of the prognostic and immunological signature of eight Tripartitemotif (TRIM) family molecules in human gliomas
- 1 Institute of Neuroscience, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China
- 2 Department of Clinical Medicine, The Second Clinical School of Guangzhou Medical University, Guangzhou 510182, China
- 3 Department of Neurosurgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan 471003, China
Received: February 13, 2023 Accepted: June 9, 2023 Published: June 24, 2023
https://doi.org/10.18632/aging.204841How to Cite
Copyright: © 2023 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: TRIM family molecules have been identified as being involved in the tumor progression of various cancer types. Increasingly, experimental evidence indicates that some of TRIM family molecules are implicated in glioma tumorigenesis. However, the diverse genomic changes, prognostic values and immunological landscapes of TRIM family of molecules have yet to be fully determined in glioma.
Methods: In our study, employing the comprehensive bioinformatics tools, we evaluated the unique functions of 8 TRIM members including TRIM5/17/21/22/24/28/34/47 in gliomas.
Results: The expression levels of 7 TRIM members (TRIM5/21/22/24/28/34/47) were higher in glioma as well as its diverse cancer subtypes than in normal tissues, whereas the expression level of TRIM17 was the opposite, lower in the former than in the latter. In addition, survival analysis revealed that the high expression profiles of TRIM5/21/22/24/28/34/47 were associated with poor overall survival (OS), disease-specific survival (DSS) and progress-free interval (PFI) in glioma patients, whereas TRIM17 displayed adverse outcomes. Moreover, the 8 TRIM molecules expression as well as methylation profiles remarkably correlated with different WHO grades. And genetic alterations, including mutations and copy number alterations (CNAs), in the TRIM family were correlated with longer OS, DSS and progress-free survival (PFS) in glioma patients. Furthermore, through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results of these 8 molecules and their related genes, we found that these molecules may change the immune infiltration of the tumor microenvironment and regulate the expression of immune checkpoint molecules (ICMs), affecting the occurrence and development of gliomas. The correlation analyses between the 8 TRIM molecules and TMB (tumor mutational burden)/MSI (microsatellite instability)/ICMs discovered that as the expression level of TRIM5/21/22/24/28/34/47 increased, the TMB score also increased significantly, while TRIM17 showed an opposite outcome. Further, a 6-gene signature (TRIM 5/17/21/28/34/47) for predicting overall survival (OS) in gliomas was built by using the least absolute shrinkage and selection operator (LASSO) regression, and the survival and time-dependent ROC analyses all were found to perform well in testing and validation cohorts. Results of multivariate COX regression analysis showed that TRIM5/28 are both expected to become independent risk predictors to guide clinical treatment.
Conclusion: In general, the results indicate that TRIM5/17/21/22/24/28/34/47 might exert a crucial influence on gliomas tumorigenesis and might be putative prognostic markers and therapeutic targets for glioma patients.
Abbreviations
aDCs: activated DCs; AUC: area under ROC curves; CRPC: castration-resistant prostate cancer; DC: dendritic cell; DSS: disease-specific survival; ESTIMATE: Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data; GBM: glioblastoma; GO: Gene Ontology; ICMs: immune checkpoint molecules; iDCs: immature DCs; KEGG: Kyoto Encyclopedia of Genes and Genomes; LGG: low-grade gliomas; MSI: microsatellite instability; OS: overall survival; pDCs: plasmacytoid DCs; PFI: progress-free interval; PFS: progress-free survival; ROC: receiver operating characteristic; ssGSEA: single-sample Gene Set Enrichment Analysis; TCGA: The Cancer Genome Atlas; Tcm: T central memory cells; Tem: T effector memory cells; Tfh: T follicular helper cells; Tgd: T gamma delta cells; TIRs: Toll-like receptors; TMB: tumor mutational burden; TRIM: Tripartite motif.