Comprehensive analysis of the prognostic and immunological signature of TNFAIP8 family genes in human glioma

Abstract

TNFAIP8 family molecules have been recognized for their involvement in the progression of tumors across a range of cancer types. Emerging experimental data suggests a role for certain TNFAIP8 family molecules in the development of glioma. Nonetheless, the comprehensive understanding of the genomic alterations, prognostic significance, and immunological profiles of TNFAIP8 family molecules in glioma remains incomplete. In the study, using the comprehensive bioinformatics tools, we explored the unique functions of 4 TNFAIP8 members including TNFAIP8, TNFAIP8L1, TNFAIP8L2 and TNFAIP8L3 in glioma. The expressions of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were notably upregulated in glioma tissues compared to normal tissues. Furthermore, survival analysis indicated that elevated expression levels of TNFAIP8, TNFAIP8L1 and TNFAIP8L2 were correlated with unfavorable outcomes in terms of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) among glioma patients. Genetic modifications, such as mutations and copy number alterations, within the TNFAIP8 family exhibited a significant association with extended OS, DSS and PFS in individuals diagnosed with glioma. The findings suggest a noteworthy correlation between TNFAIP8 family members and the age and 1p/19q codeletion status of glioma patients. We also found that there were significant relationships between TNFAIP8 family expression and tumor immunity in glioma. Furthermore, functional annotation of TNFAIP8 family members and their co-expressed genes in gliomas was carried out using GO and KEGG pathway analysis. The GO analysis revealed that the primary biological processes influenced by the TNFAIP8 family co-expressed genes included cell chemotaxis, temperature homeostasis, and endocytic vesicle formation. Additionally, the KEGG analysis demonstrated that TNFAIP8 family co-expressed genes are involved in regulating various pathways such as inflammatory mediator regulation of TRP channels, pathways in cancer, prolactin signaling pathway, and Fc gamma R-mediated phagocytosis. Overall, the findings suggest that TNFAIP8 family members may play a significant role in the development of glioma and have the potential to serve as prognostic indicators and therapeutic targets for individuals with glioma.

Keywords: Glioma; Immunological signature; Prognostic; TNFAIP8 family.

Figure 1

The expression, Survival analysisand The area under the curve values for receiver operator characteristic (ROC) curves of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 in glioma tissue and normal tissue. 1A: The expression of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 in glioma tissue and normal tissue (***p < 0.001). 1B-1 M: Survival analysis of TNFAIP8 family members in glioma patients. The overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) survival curves comparing patients with high and low TNFAIP8 family members expression in gliomas are shown Fig. 1N-1Q: The area under the curve values for receiver operator characteristic (ROC) curves for TNFAIP8 family members across glioma (A-D).

Figure 2

A logistic regression analysis was conducted between TNFAIP8 family members and clinicopathological parameters among patients with glioma.

Figure 3

Genetic alterations in TNFAIP8 family members and their relationship with prognosis of glioma patients. Summary of alterations in different expressed TNFAIP8 families in glioma (A, B). Associations of different TNFAIP8 family members with each other (C). Genetic alterations in TNFAIP8 family were correlated to longer overall survival (OS) (D), disease-specific survival (DSS) (E), and progress-free interval (PFI) (F) of glioma patients.

Figure 4

TNFAIP8 family expressions and tumor immunity. In the bar graph, TNFAIP8 (A), TNFAIP8L1 (B), TNFAIP8L2 (C) and TNFAIP8L3 (D) expressions were correlated with 24 immune infiltration cells. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 5

The relationships between the enrichment of immune cells and TNFAIP8 family (A-D) high and low expression groups of glioma. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 6

Correlation analyses of the expression profiles of TNFAIP8 family with immune checkpoint molecules in glioma and genes co-expressed with TNFAIP8 family in glioma.. 6A:The horizontal and vertical ordinates represent genes, and different colors represent correlation coefficients (in the diagram, red represents positive correlation, blue represents negative correlation) Fig. 6B-E showed the top 10 co-expressed genes correlated with TNFAIP8 family positively and negatively. Moreover, the 12 intersections among TNFAIP8 family co-expressing genes (including CORO1A, OSTF1, TM6SF1, TNFRSF11A, KCNK13, PRKCD, STAT6, PIK3CD, FMNL1, FFAR4, TRPV2 and RASSF5) are shown in a Venn diagram (F). We conducted a comprehensive correlation analysis to further explore the relationship between TNAIP8 family expressions and the 12 co-expressing genes (G). *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 7

Gene Ontologies (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of TNFAIP8 family members and their co-expression genes in glioma. Bubble charts of GO (A) and KEGG (B) terms.