ArticleFrontiers in pharmacology2025
The role of TRAF2 in pan-cancer revealed by integrating informatics and experimental validation.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Tumor necrosis factor (TNF) receptor associated factor-2 (TRAF2) is an E3 ubiquitin ligase and scaffolding protein that contribute to the progression of various malignant tumors. However, the role of TRAF2 expression in epigenetic, cancer prognosis, and immune responses in tumor microenvironment is unclear. Methods: We used The Human Protein Atlas (HPA) database, TIMER 2.0 database, and TCGA database to evaluate TRAF2 expression in human normal and tumor tissues. Correlation of TRAF2 expression with mutations and epigenetic in tumors was evaluated using the cBioPortal platform and the GSCA database. To assess the prognostic value of TRAF2, we performed Kaplan-Meier plots and Cox regression analysis. LinkedOmics database was used for PANTHER Pathways enrichment analysis. The relationship between TRAF2 expression and immune checkpoint genes, as well as immune cell infiltration, was examined using TIMER 2.0 and the R language. Single-cell sequencing data and multiple immunofluorescence staining were used to observe the co-expression of TRAF2 on hepatocellular carcinoma cells and immune cells. Furthermore, using siRNA-mediated knockdown, we explored the potential role of TRAF2 in liver cancer cell biology. Results: Our findings indicate that TRAF2 is frequently mutated and significantly overexpressed in various types of cancers, and this overexpression is linked to a poor prognosis. The epigenetic alterations in TRAF2 was significant across various types of cancers. TRAF2 is associated with the levels of various immune checkpoint genes and multiple tumor-infiltrating immune cells, suggesting its potential involvement in tumor microenvironment. Of note, enrichment analysis revealed a significant correlation between TRAF2 and T cell activation, and single-cell sequencing indicated that TRAF2 was overexpressed in malignant cells and T cells. Conclusion: TRAF2 represents a potential prognostic biomarker and therapeutic target for cancer immunotherapy, particularly in patients with hepatocellular carcinoma.
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