Elevated TNFRSF4 gene expression is a predictor of poor prognosis in non-M3 acute myeloid leukemia

Abstract

We used bioinformatic tools to dichotomize 157 non-M3 AML patients from the TCGA dataset based on the presence or absence of TP53 mutations, and screened out a key gene related to TP53 mutation for future analysis. DEGs were analyzed by R package “DESeq2” and then run GSEA, GO enrichment, KEGG pathway and PPI network. Hub genes were selected out according to MCC. Log-rank (Mantel–Cox) test was used for survival analysis. Mann–Whitney U’s nonparametric t test and Fisher’s exact test was used for continuous and categorical variables respectively. p value< 0.05 was considered to be statistical significance. TNFRSF4 was final screened out as a key gene. Besides TP53 mutation (p = 0.0118), high TNFRSF4 was also associated with FLT3 mutation (p = 0.0102) and NPM1 mutation (p = 0.0024). Elevated TNFRSF4 was significantly related with intermediate (p = 0.0004) and poor (p = 0.0011) risk stratification as well as relapse statute (p = 0.0099). Patients with elevated TNFRSF4 expression had significantly shorter overall survival (median survival: 2.35 months vs. 21 months, p < 0.0001). Based on our clinical center data, TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs (p = 0.0377) and MDS patients (EB-1, 2; p = 0.0017). Elevated TNFRSF4 expression was associated with TP53, FLT3 and NPM1 mutation as well as poor clinical outcome. TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs and MDS (EB-1, 2) patients. TNFRSF4 is need for future functional and mechanistic studies to investigate the role in non-M3 AML.