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...
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Springer
2025-05-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02511-5 |
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| author | Xuezhong Zhang Min Qu Lei Bi Xiaolei Wang Tonggang Liu |
| author_facet | Xuezhong Zhang Min Qu Lei Bi Xiaolei Wang Tonggang Liu |
| author_sort | Xuezhong Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2d22347912fa456ca1ba00a38ad78d4e |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-2d22347912fa456ca1ba00a38ad78d4e2025-08-20T01:49:36ZengSpringerDiscover Oncology2730-60112025-05-0116111610.1007/s12672-025-02511-5Expression patterns, prognostic significance, and immune correlations of the TNFAIP8 family in acute myeloid leukemia: a comprehensive bioinformatics analysisXuezhong Zhang0Min Qu1Lei Bi2Xiaolei Wang3Tonggang Liu4Department of Laboratory Medicine, Zibo Central HospitalDepartment of Laboratory Medicine, Zibo First HospitalDepartment of Laboratory Medicine, Zibo Central HospitalDepartment of Public Health, Zibo Central HospitalDepartment of Infectious Diseases, Binzhou Medical University HospitalAbstract 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.https://doi.org/10.1007/s12672-025-02511-5Acute Myeloid Leukemia (AML)TNFAIP8 FamilySurvival AnalysisReceiver Operating Characteristic (ROC) AnalysisBiomarkersFunctional Analysis |
| spellingShingle | Xuezhong Zhang Min Qu Lei Bi Xiaolei Wang Tonggang Liu Expression patterns, prognostic significance, and immune correlations of the TNFAIP8 family in acute myeloid leukemia: a comprehensive bioinformatics analysis Discover Oncology Acute Myeloid Leukemia (AML) TNFAIP8 Family Survival Analysis Receiver Operating Characteristic (ROC) Analysis Biomarkers Functional Analysis |
| title | Expression patterns, prognostic significance, and immune correlations of the TNFAIP8 family in acute myeloid leukemia: a comprehensive bioinformatics analysis |
| title_full | Expression patterns, prognostic significance, and immune correlations of the TNFAIP8 family in acute myeloid leukemia: a comprehensive bioinformatics analysis |
| title_fullStr | Expression patterns, prognostic significance, and immune correlations of the TNFAIP8 family in acute myeloid leukemia: a comprehensive bioinformatics analysis |
| title_full_unstemmed | Expression patterns, prognostic significance, and immune correlations of the TNFAIP8 family in acute myeloid leukemia: a comprehensive bioinformatics analysis |
| title_short | Expression patterns, prognostic significance, and immune correlations of the TNFAIP8 family in acute myeloid leukemia: a comprehensive bioinformatics analysis |
| title_sort | expression patterns prognostic significance and immune correlations of the tnfaip8 family in acute myeloid leukemia a comprehensive bioinformatics analysis |
| topic | Acute Myeloid Leukemia (AML) TNFAIP8 Family Survival Analysis Receiver Operating Characteristic (ROC) Analysis Biomarkers Functional Analysis |
| url | https://doi.org/10.1007/s12672-025-02511-5 |
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