Implications of a splicing variant of AIMP2 lacking exon 2 among various cancer types including acute myelogenous leukemia

Abstract

Aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) is a potent tumor suppressor. An exon-2 depleted splicing variant ofAIMP2 (AIMP2-DX2) is responsible for tumorigenesis by compromising the tumor suppressive activity of AIMP2. This study aimed to investigate the role ofAIMP2-DX2 over diverse cancers using whole transcriptome data in The Cancer Genome Atlas (TCGA), and International Cancer Genome Consortium (ICGC) database. A total of 753 samples were analyzed for the presence of AIMP2-DX2 and its prognostic role in various cancers. AIMP2-DX2 was universally expressed to varying degrees, with a prognostic implication in several cancers. In acute myemyeloid leukemia (AML), AIMP2-DX2/AIMP2 ratio was strongly correlated with major cancer signaling pathways, and had a tendency toward exhibiting poor prognosis (Log rank P=0.16). We validated the prognostic implication of AIMP2-DX2 using AML patient samples. For 51 AML patients, overall survival (OS) and progression-free survival (PFS) of AIMP2-DX2 positive patients were significantly inferior to that of AIMP2-DX2 negative patients (for OS: hazard ratio [HR] 2.47

95% confidence interval [CI] 1.14–5.34

P=0.022

for PFS: HR 2.59

95% CI 1.32–5.11

P=0.006). Collectively, AIMP2-DX2 may be a novel biomarker and a potential therapeutic target for AML.