<i>PLA2G4A</i> Is a Potential Biomarker Predicting Shorter Overall Survival in Patients with Non-M3/ <i>NPM1</i> Wildtype Acute Myeloid Leukemia

Abstract

In this study, we aimed at exploring and validating the prognostic value of <i>PLA2G4A</i> expression in patients with non-M3/nucleophosmin (<i>NPM1</i>) wildtype (WT) acute myeloid leukemia (AML) by using two independent datasets. Data from the Cancer Genome Atlas-acute myeloid leukemia (TCGA-LAML) and the therapeutically applicable research to generate effective treatments (TARGET)-AML were used to assess the prognostic value of <i>PLA2G4A</i> in <i>NPM1</i>-WT AML cases. Results showed that non-M3 AML cases had significantly increased <i>PLA2G4A</i> expression compared with normal peripheral blood samples. Patients with high <i>PLA2G4A</i> expression (separated by median gene expression) had a significantly shorter overall survival (OS) compared with the group with low <i>PLA2G4A</i> expression, in both TCGA-LAML and TARGET-AML. Multivariate analysis showed that high <i>PLA2G4A</i> expression was independently associated with shorter OS in 97 non-M3/<i>NPM1</i>-WT AML cases in TCGA-LAML (hazard ratio [HR]: 1.946, 95% confidence interval [CI]: 1.094-3.462, <i>q</i> = 0.036). The prognostic value was validated based on 120 primary non-M3/<i>NPM1</i>-WT AML cases in TARGET-AML (HR: 1.518, 95% CI: 1.037-2.223, <i>q</i> = 0.048). Therefore, <i>PLA2G4A</i> expression might serve as an independent prognostic marker in OS in patients with non-M3/<i>NPM1</i> WT AML. Bioinformatic analysis identified that several proteins physically interacted with <i>PLA2G4A</i>, some of which have well-characterized oncogenic properties in AML, such as RUVBL2, cytoskeleton regulatory protein 1 (CAP1), signal transducer and activator of transcription 3 (STAT3), and MYCBP. Therefore, we hypothesized that <i>PLA2G4A</i> upregulation has multiple effects on the malignant phenotype of AML cells together with its partners. Future molecular studies are required to explore the detailed regulatory network involved.