TNFAIP6, an independent prognostic monitor and therapy target, promoted low-grade glioma recurrence and progression via JAK3-STAT6 signaling.

BACKGROUND: Low-grade glioma (LGG, WHO2-3 grade), a kind of common primary tumor of the central nervous system, exhibits high 5-year survival rates but frequently recurs and progresses to higher-grade tumors, leading to poor prognosis. Effective prognostic biomarkers and therapeutic targets are urgently needed. Tumor necrosis factor alpha-induced proteins (TNFAIPs), key regulators within the inflammatory microenvironment, have been proven to play an important role in regulating tumor invasion and metastasis via immunoinflammatory suppression. Nevertheless, their functional mechanism and clinical significance in LGG remained unclear. Lacking studies focused on the direct effects of TNFAIPs themselves on regulating the malignant biological behaviors of LGG. MATERIALS AND METHODS: In this study, we employed bioinformatics analysis, machine learning algorithms, and in vitro cell experiments to investigate the potential effects of TNFAIP6 on LGG. RESULTS: It found that TNFAIP6 can be a reliable prognostic marker for LGG, which directly regulates the malignant behaviors of LGG, including proliferation, invasion, and migration, thereby promoting LGG recurrence and progression. These processes were proven to be closely associated with the activation of the JAK3-STAT6 signaling pathway. CONCLUSION: Our findings demonstrated that TNFAIP6 can directly contribute to the malignant behaviors of LGG, providing a theoretical basis for developing targeted therapeutic strategies against TNFAIP6 and the JAK3-STAT6 signaling axis in LGG.