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Abstract

Introduction

Sarcomas are heterogeneous mesenchymal tumors with poor responses to systemic therapies. Ubiquitination is a post-translational modification that regulates various physiological processes and cancer growth.

Methods

We analyzed the transcriptomic data of 256 sarcoma patients from The Cancer Genome Atlas (TCGA) to define the network and prognostic value of predefined ubiquitination-related genes and performed subgroup analyses. Additionally, the role of TRIM21 in sarcoma progression was explored using cellular experiments.

Results

We identified two ubiquitination-related clusters, and patients in the two clusters were characterized by different survival outcomes, enriched pathways, and characteristics of the tumor microenvironment. A ubiquitination-related signature involving LRRC41, RNF125, TRIM21, and UBE3D was identified to predict prognoses. The signature was associated with patient prognoses in the public sarcoma cohorts and our independent cohort. Immunohistochemistry analyses revealed that the risk score and CD8 could distinguish patients with different survival outcomes in our cohort. Mechanistically, different risk groups were also characterized by distinct enriched pathways and characteristics of the tumor microenvironment. Cellular experiments revealed that TRIM21 overexpression could suppress tumor progression in sarcomas.

Discussion

This study provided a novel classification for sarcoma patients based on expressions of ubiquitination-related genes. The classification and the prognostic model may facilitate the understanding of sarcoma pathogenesis, the prediction of prognosis and immunotherapy response for sarcoma patients. Meanwhile, it was confirmed that TRIM21 suppressed sarcoma progression and identified it as a potential target for therapeutic interventions.

Conclusion

The classification and signature stratify sarcoma patients for prognosis and immunotherapy response, with TRIM21 representing a promising therapeutic target.

© 2026 Bentham Science Publishers
© 2026 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2026-01-15
2026-02-26

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/content/journals/cmc/10.2174/0109298673388379251113061745
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Ubiquitination-based Classification and a Prognostic Signature Identify the Role of TRIM21 in Sarcoma Progression
Bentham Science Publishers ; https://doi.org/10.2174/0109298673388379251113061745
/content/journals/cmc/10.2174/0109298673388379251113061745
/content/journals/cmc/10.2174/0109298673388379251113061745
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  • Article Type:     Research Article
Keywords: Sarcomas ; tumor microenvironment ; TCGA ; ubiquitination ; TRIM21 ; prognosis

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