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Updated: Nov 21, 2025
Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
High TRAF3IP3 Level Predicts Poor Prognosis of Patients with Gliomas
Guorong Yang1, Shu Tang1, Jie Zhang1
1Department of Oncology, The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, China.
Background:
Tumor necrosis factor receptor-related factor 3 (TRAF3) interacting protein 3 (TRAF3IP3) is involved in the development of immune tissues and the immune response of the body. Downregulated expression of TRAF3IP3 in malignant melanoma can inhibit tumor growth. The role of TRAF3IP3 in glioma is unknown.
Methods:
We used the Wilcoxon rank sum test to compare the expression of TRAF3IP3 in glioma and normal tissues based on The Cancer Genome Atlas and Genotype Tissue Expression. Logistics regression was used to evaluate the relationship between TRAF3IP3 and clinicopathologic characters. Gene set enrichment analysis and single-sample gene set enrichment analysis were conducted to annotate biological function of TRAF3IP3. We used Kaplan-Meier and Cox regression to evaluate the prognostic value of TRAF3IP3.
Results:
We downloaded RNA-seq data of 670 gliomas and 1157 normal tissues. TRAF3IP3 was highly expressed in gliomas (P < 0.001). High expression of TRAF3IP3 and higher World Health Organization grade (odds ratio [OR], 3.57 [2.42-5.34 CI]; P < 0.001), wild-type isocitrate dehydrogenase status (OR, 4.79 [3.40-6.83 CI]; P < 0.001), 1p/19q non-codeletion (OR, 15.32 [9.23-27.01 CI]; P < 0.001), mutant epidermal growth factor receptor status (OR, 2.77 [1.65-4.81 CI]; P < 0.001), worse histologic type (OR, 3.64 [2.48-5.43 CI]; P < 0.001) and worse primary therapy outcome (OR, 2.29 [1.47-3.61 CI]; P < 0.001) were significantly correlated. Six signaling pathways were significantly enriched in the TRAF3IP3 high-expression phenotype group, including JAK-STAT, interferon-γ, apoptosis, P53, programmed cell death protein 1, and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4). High expression of TRAF3IP3 was associated with worse progression-free survival (hazard ratio [HR], 2.39 (1.39-3.01); P < 0.001), disease-free survival (HR, 3.02 (2.27-4.01); P < 0.001) and overall survival (HR, 2.87 (2.20-3.75); P < 0.001).
Conclusions:
TRAF3IP3 play an important role in the occurrence and development of glioma and may be a potential biomarker for the prognosis of glioma.
Insights
Tumor necrosis factor receptor-associated factor 3 (TRAF3) interacting protein 3 (TRAF3IP3) is highly expressed in gliomas and associated with poorer survival. TRAF3IP3 may serve as a prognostic biomarker for glioma patients.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Tumor necrosis factor receptor-associated factor 3 (TRAF3) interacting protein 3 (TRAF3IP3) is implicated in immune tissue development and immune responses.
- While TRAF3IP3 downregulation inhibits melanoma growth, its role in glioma remains unexplored.
Purpose of the Study:
- To investigate the expression levels of TRAF3IP3 in glioma tissues compared to normal tissues.
- To analyze the correlation between TRAF3IP3 expression and clinicopathological features of glioma.
- To evaluate the prognostic significance of TRAF3IP3 in glioma.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases for RNA-seq data analysis.
- Employed Wilcoxon rank sum test for expression comparison, logistic regression for clinicopathological correlations, and GSEA for functional annotation.
- Kaplan-Meier and Cox regression analyses were performed to assess prognostic value.
Main Results:
- TRAF3IP3 was significantly upregulated in 670 gliomas compared to 1157 normal tissues (P < 0.001).
- High TRAF3IP3 expression correlated with advanced World Health Organization grade, wild-type isocitrate dehydrogenase, 1p/19q non-codeletion, mutant epidermal growth factor receptor, unfavorable histologic type, and poorer therapy outcomes.
- Enriched pathways included JAK-STAT, interferon-γ, apoptosis, P53, PD-1, and CTLA-4. High TRAF3IP3 expression predicted worse progression-free, disease-free, and overall survival (P < 0.001).
Conclusions:
- TRAF3IP3 plays a significant role in glioma development and progression.
- TRAF3IP3 is a potential prognostic biomarker for glioma.
