High expression of miR-363 predicts poor prognosis and guides treatment selection in acute myeloid leukemia

Abstract

Abstract Background Acute myeloid leukemia (AML) is a highly heterogeneous malignancy with various outcomes, and therefore needs better risk stratification tools to help select optimal therapeutic options. Methods In this study, we identify miRNAs that could predict clinical outcome in a heterogeneous AML population using TCGA dataset. Results We found that MiR-363 is a novel prognostic factor in AML patients undergoing chemotherapy. In multivariable analyses, high miR-363 remained predictive for shorter OS (HR = 2.349, P = 0.012) and EFS (HR = 2.082, P = 0.001) independent of other well-known prognostic factors. More importantly, allogeneic hematopoietic stem cell transplantation (allo-HSCT) overcame the adverse outcomes related to high miR-363 expression. In gene expression profiling, high miR-363 expression was positively correlated with the amounts of leukemogenic transcription factors, including Myb, RUNX3, GATA3, IKZF3, ETS1 and MLLT3. Notably, we found that the in silico predicted target genes (EZH2, KLF6 and PTEN) of miR-363 were downregulated in association with high miR-363 expression. Conclusions In summary, miR-363 expression may help identify patients in need of strategies to select the optimal therapy between chemotherapeutic and allo-HCST regimens. AML patients with high miR-363 expression may be highly recommended for early allo-HSCT regimen.

Keywords

• Mir-363
• Acute myeloid leukemia
• Clinical outcome
• Chemotherapy
• Allo-HSCT