Expression patterns, prognostic significance, and immune correlations of the TNFAIP8 family in acute myeloid leukemia: a comprehensive bioinformatics analysis

Abstract

Background: Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with poor prognosis and high relapse rates. While the TNFAIP8 gene family (TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3) is implicated in cancer and immune regulation, its role in AML remains unclear. This study utilized bioinformatics analyses to investigate their expression, prognostic significance, genetic alterations, and immune associations in AML.

Methods: The expression levels and clinical significance of TNFAIP8 family genes in AML were evaluated using UCSC XENA databases. Kaplan-Meier survival analysis was performed to assess overall survival (OS) differences, and receiver operating characteristic (ROC) curves were utilized to evaluate the prognostic predictive abilities of these genes. Genetic alterations were analyzed using the cBioPortal platform, while immune infiltration was examined through ssGSEA and Spearman correlation analysis. Functional enrichment analysis of co-expressed genes was conducted using the KEGG and GO databases.

Results: TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were significantly overexpressed in AML tissues compared to normal tissues (P < 0.001). However, Kaplan-Meier survival analysis revealed no significant association between their expression levels and OS in AML patients. ROC curve analysis showed that TNFAIP8L2 had the highest predictive accuracy (AUC = 1.000) among the family members, followed by TNFAIP8L1 (AUC = 0.728), TNFAIP8 (AUC = 0.709), and TNFAIP8L3 (AUC = 0.629). Clinicopathological analysis indicated that TNFAIP8 and TNFAIP8L1 expressions were associated with poor cytogenetic risk, while TNFAIP8L3 expression correlated strongly with elevated bone marrow blasts (P < 0.001). Mutation analysis revealed a low frequency of genetic alterations, with TNFAIP8L1 being the only gene with mutations in 0.53% of cases. Immune infiltration analysis demonstrated that TNFAIP8 and TNFAIP8L3 were positively correlated with myeloid-derived suppressor cells (MDSCs), while TNFAIP8L1 expression was associated with natural killer (NK) cell enrichment.

Conclusion: TNFAIP8 family genes play distinct roles in AML pathogenesis and immune regulation. TNFAIP8L2 shows promise as a prognostic biomarker, while TNFAIP8 and TNFAIP8L1 may indicate adverse cytogenetic risk. The study highlights their potential as therapeutic targets in AML.

Keywords: Acute Myeloid Leukemia (AML); Biomarkers; Functional Analysis; Receiver Operating Characteristic (ROC) Analysis; Survival Analysis; TNFAIP8 Family.

Fig. 1

Comparison of expression levels of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 in AML tissues versus normal tissues. ***P < 0.001

Fig. 2

Survival analysis in AML patients based on TNFAIP8 family gene expression. The survival curves display overall survival (OS) contrasting patients with high versus low expression levels of TNFAIP8 family genes (A–D)

Fig. 3

Receiver operating characteristic (ROC) curve analysis for TNFAIP8 family members in AML, indicating the area under the curve (AUC) values (A–D)

Fig. 4

Genetic alterations in the TNFAIP8 family and their prognostic associations in AML patients. This includes a summary of the differentially expressed TNFAIP8 family genes in AML (A, B) and their interrelationships (C)

Fig. 5

TNFAIP8 family expression and its association with tumor immunity in AML. The bar graph presents the relationship between TNFAIP8 (A), TNFAIP8L1 (B), TNFAIP8L2 (C), and TNFAIP8L3 (D) expression levels and the infiltration of 24 distinct immune cells in AML. *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 6

Evaluation of immune cell infiltration in relation to TNFAIP8 family gene expression in AML. The plots depict groups with high and low expression of TNFAIP8 family members (A–D) in connection with immune cell enrichment. *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 7

The correlation analysis between TNFAIP8 family genes levels and immune checkpoints in LAML. *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 8

The top 5 genes that are positively and negatively correlated with the TNFAIP8 (A), TNFAIP8L1 (B), TNFAIP8L2 (C), and TNFAIP8L3 (D) in AML, respectively. *P < 0.05, **P < 0.01, ***P < 0.001

Fig. 9

Co-expression analysis of TNFAIP8 family genes in AML, including Gene Ontology (GO) and KEGG enrichment analysis. The Venn diagram shows the overlap of co-expressing genes (A), while bubble charts represent GO (B) and KEGG (C) enrichment terms