Pan-cancer illumination of TRIM gene family reveals immunology regulation and potential therapeutic implications

Gao, Yueying; Pan, Tao; Xu, Gang; Li, Si; Guo, Jing; Zhang, Ya; Xu, Qi; Pan, Jiwei; Ma, Yanlin; Xu, Juan; Li, Yongsheng

doi:10.1186/s40246-022-00441-9

Cited by 3 publications

(2 citation statements)

References 66 publications

(67 reference statements)

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“… 39 TRIM scores were reported to be significantly associated with immune cells, especially follicular helper T cells, CD8(+) T cells, activated NK cells, and M1 and M2 macrophages, in cancer. 40 Immune cells play a crucial role in viral infection, and given that the TRIM5-encoding protein is associated with viruses, TRIM5 may function in SLE through the regulation of immune cells. TRIM5’s restriction role was in a cell-type specific manner, which has been revealed by HIV-1 infection.…”

Section: Discussionmentioning

confidence: 99%

TRIM5 Promotes Systemic Lupus Erythematosus Through CD4(+) T Cells and Macrophage

Pan,

Yang,

Zhang

et al. 2023

IJGM

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Purpose Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by the involvement of multiple organs and the production of antinuclear antibodies. This study aimed to investigate the molecular mechanism of SLE. Patients and Methods We retrieved genome-wide gene expression levels from five public datasets with relatively large sample sizes from the Gene Expression Omnibus (GEO), and we compared the expression profiles of peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls (HCs). The expression of seven target genes in PBMCs from 25 cases and 3 HCs was further validated by reverse-transcription quantitative PCR (RT‒qPCR). Flow cytometry was used for verifying the proportion of naive CD4(+) T cells and M2 macrophages in PBMCs from 5 cases and 4 HCs. Results We found 14 genes (TRIM5, FAM8A1, SHFL, LHFPL2, PARP14, IFIT5, PARP12, DDX60, IRF7, IF144, OAS1, OAS3, RHBDF2, and RSAD2) that were differentially expressed among all five datasets. The heterogeneity test under the fixed effect model showed no obvious heterogeneity of TRIM5, FAM8A1, and SHFL across different populations. TRIM5 was positively correlated with the remaining 13 genes. By separating patient samples into TRIM5-high and TRIM5-low groups, we found that up-regulated genes in the TRIM5-high group were mainly enriched in virus-related pathways. Immune cell proportion analysis and flow cytometry revealed that naive CD4(+) T cells were significantly decreased while M2 macrophages were increased in the SLE group. TRIM5 expression levels were negatively correlated with naive CD4(+) T cells but positively correlated with M2 macrophages. Conclusion Our data indicated that TRIM5 might be a key factor that modulates SLE etiology, possibly through naive CD4(+) T cells and M2 macrophages.

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Section: Discussionmentioning

confidence: 99%

TRIM5 Promotes Systemic Lupus Erythematosus Through CD4(+) T Cells and Macrophage

Pan,

Yang,

Zhang

et al. 2023

IJGM

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“…Conducting pan-cancer analysis of gene families allows for a holistic understanding of shared genetic alterations or discerning context-specific variations, uncovering divergent roles across cancer types and informing targeted therapeutic strategies tailored to the unique characteristics of individual genes within the family 30,31 . We also conducted a comprehensive pancancer analysis of kindlin genes using data from the TCGA, COSMIC, and ICGC databases across 33 cancer types (Supplementary Note 1) [32][33][34] .…”

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confidence: 99%

Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations

Chowdhury,

Mistry,

Maity

et al. 2024

Commun Biol

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Kindlins serve as mechanosensitive adapters, transducing extracellular mechanical cues to intracellular biochemical signals and thus, their perturbations potentially lead to cancer progressions. Despite the kindlin involvement in tumor development, understanding their genetic and mechanochemical characteristics across different cancers remains elusive. Here, we thoroughly examined genetic alterations in kindlins across more than 10,000 patients with 33 cancer types. Our findings reveal cancer-specific alterations, particularly prevalent in advanced tumor stage and during metastatic onset. We observed a significant co-alteration between kindlins and mechanochemical proteome in various tumors through the activation of cancer-related pathways and adverse survival outcomes. Leveraging normal mode analysis, we predicted structural consequences of cancer-specific kindlin mutations, highlighting potential impacts on stability and downstream signaling pathways. Our study unraveled alterations in epithelial–mesenchymal transition markers associated with kindlin activity. This comprehensive analysis provides a resource for guiding future mechanistic investigations and therapeutic strategies targeting the roles of kindlins in cancer treatment.

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Comprehensive Analysis of TRIM Family-based Signature in LUAD Progression and Immunotherapy

Han,

Liu,

Shan

et al. 2023

Preprint

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Purpose: Within the ubiquitination process, E3 ligases function profoundly since they decide the final step of target specificity. As the largest subfamily of E3 ligases, tripartite motif (TRIM) family genes play pivotal roles in tumor progression and immune response, however, lacking systematic exploration of the expression patterns and clinical correlations in lung adenocarcinoma (LUAD). We aim to comprehensively analyze the TRIM expression profile in LUAD and establish a TRIM family–based prognostic risk model. Methods: We enrolled 1299 cases from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets for risk model training and validation. Another 38 LUAD tissues were collected for validation. Bioinformatic methods and immunofluorescent staining were utilized to illustrated the related Biological characteristics, mutation tendency, immune profile and predicted immunotherapy response. Results: After Cox proportional hazards regression analyses, we established a 3 TRIM gene-based risk model by TCGA dataset. The risk model divided patients into high and low score groups showing different overall survival (OS), being an independent prognostic factor irrespective of other clinical features. And the stability was estimated in GEO validation datasets and even tissues at protein level. Further explorations demonstrated patients within high risk group showed tendency to more EGFR mutation and severer immune suppressive status. Moreover, the risk model was markedly correlated with diverse immunotherapy response markers. Conclusion: We constructed the first TRIM-based prognostic risk model for LUAD OS prediction and demonstrated the relationships between the model and LUAD immune characteristics. The risk model might assist the clinical application of immunotherapies.

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Pan-cancer illumination of TRIM gene family reveals immunology regulation and potential therapeutic implications

Cited by 3 publications

References 66 publications

TRIM5 Promotes Systemic Lupus Erythematosus Through CD4(+) T Cells and Macrophage

TRIM5 Promotes Systemic Lupus Erythematosus Through CD4(+) T Cells and Macrophage

Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations

Comprehensive Analysis of TRIM Family-based Signature in LUAD Progression and Immunotherapy

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