Pan-cancer analysis of oncogenic TNFAIP2 identifying its prognostic value and immunological function in acute myeloid leukemia

Abstract

AbstractBackgroundTumor necrosis factor alpha-induced protein 2 (TNFAIP2), a TNFα-inducible gene, appears to participate in inflammation, immune response, hematopoiesis, and carcinogenesis. However, the potential role ofTNFAIP2in the development of acute myeloid leukemia (AML) remains unknow yet. Therefore, we aimed to study the biological role ofTNFAIP2in leukemogenesis.MethodsTNFAIP2mRNA level, prognostic value, co-expressed genes, differentially expressed genes, DNA methylation, and functional enrichment analysis in AML patients were explored via multiple public databases, including UALCAN, GTEx portal, Timer 2.0, LinkedOmics, SMART, MethSurv, Metascape, GSEA and String databases. Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Beat AML database were used to determine the associations betweenTNFAIP2expression and various clinical or genetic parameters of AML patients. Moreover, the biological functions ofTNFAIP2in AML were investigated through in vitro experiments.ResultsBy large-scale data mining, our study indicated thatTNFAIP2was differentially expressed across different normal and tumor tissues.TNFAIP2expression was significantly increased in AML, particularly in French–American–British (FAB) classification M4/M5 patients, compared with corresponding control tissues. Overexpression ofTNFAIP2was an independent poor prognostic factor of overall survival (OS) and was associated with unfavorable cytogenetic risk and gene mutations in AML patients. DNA hypermethylation ofTNFAIP2at gene body linked to upregulation ofTNFAIP2and inferior OS in AML. Functional enrichment analysis indicated immunomodulation function and inflammation response ofTNFAIP2in leukemogenesis. Finally, the suppression ofTNFAIPresulted in inhibition of proliferation by altering cell-cycle progression and increase of cell death by promoting early and late apoptosis in THP-1 and U937AML cells.ConclusionCollectively, the oncogenicTNFAIP2can function as a novel biomarker and prognostic factor in AML patients. The immunoregulation function ofTNFAIP2warrants further validation in AML.