Human pan-cancer analysis of the predictive biomarker for the tumor necrosis factor-alpha-induced protein 8-like 2 (TNFAIP8L2)

Abstract

Abstract Background: TNFAIP8L2 is a member of the tumor necrosis factor-alpha-inducible protein 8 (TNFAIP8) family shown to have oncogenic effects. However, no pan-cancer analysis has shown an association between TNFAIP8L2 and various tumor types. Methods: Using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other bioinformatics tools, we performed a pan-cancer analysis of the TNFAIP8L2 gene. We investigated TNFAIP8L2’s function in 33 tumor types, exploring its gene expression, survival status, DNA methylation, genetic alterations, immune infiltration, and associated cellular pathways. Results: TNFAIP8L2 was strongly expressed in most malignancies and linked with patients' overall survival (OS) and disease-free survival (DFS). Missense mutations are the main type of mutation in the TNFAIP8L2 gene. TNFAIP8L2’s methylation levels were significantly different between tumors and normal tissues. In addition, infiltration of CD8+ T cells, cancer-associated fibroblasts, and macrophages has been linked to TNFAIP8L2 expression in various malignancies, including cervical cancer, breast-infiltrating cancer, and renal clear cell carcinoma. Mechanistically, Rac2, actin filament, and Fc gamma R-mediated phagocytosis are all implicated. Conclusion: TNFAIP8L2 may be a biomarker or treatment target for predicting the prognosis of cancer victims. In addition, it might interfere with Rac2-mediated pathways regulating macrophage M1 to M2 differentiation and metastasis. This could provide a new direction for tumor therapy.