TRAF2 Expression and Its Prognostic Significance in Tumor Microenvironments: A Comprehensive Analysis
Description
Tumor necrosis factor (TNF) receptor associated factor-2 (TRAF2) is an E3 ubiquitin ligase and scaffolding protein known to contribute to the progression of various malignant tumors. However, the relationship between TRAF2 expression and gene methylation, cancer prognosis, and immune responses in the tumor microenvironment is unclear. We found that TRAF2 is significantly overexpressed in 17 different cancer types and is strongly associated with a poor prognosis. In addition, TRAF2 was found to be strongly associated with immune cell infiltration in the tumor microenvironment and the efficacy of immunotherapy, specifically in terms of a strong association with T cells. The results of our in vitro experimental studies confirmed that the loss of TRAF2 function inhibits the malignant biological behavior of HepG2 cells in hepatocellular carcinoma. This study emphasizes the potential of TRAF2 as a promising prognostic biomarker and a potential target for cancer immunotherapy, especially benefiting patients with hepatocellular carcinoma.
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We used the HPA database, the TIMER 2.0 database, and the TCGA database to detect TRAF2 expression in human normal and tumor tissues. Correlation of TRAF2 expression with mutations and methylation in tumors was detected 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 for PANTHER Pathways enrichment analysis. The relationship between TRAF2 expression and immune checkpoint genes, as well as immune 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.
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Funding
National Natural Science Foundation of China
8227150213
Natural Science Foundation of Hebei Province
H2023206137
Hebei Province Traditional Chinese Medicine Scientific Research Subjects Programme
2024110
Hebei Province Young Top Talents Programme
BJK2024036
Natural Science Foundation of Hebei Province
H2023209036