Abnormal expression and methylation of PRR34‐AS1 are associated with adverse outcomes in acute myeloid leukemia

Abstract

Abstract It was previously reported that PRR34‐AS1 was overexpressed in some solid tumors. PRR34‐AS1 promoter was shown to have a differential methylation region (DMR), and was hypomethylated in acute myeloid leukemia (AML). Therefore, the present study used real‐time quantitative PCR (RQ‐PCR) to explore the expression characteristics of PRR34‐AS1 in AML. In addition, the correlation between the expression of PRR34‐AS1 and clinical prognosis of AML was determined. The findings of this study indicated that high PRR34‐AS1 expression was bound up with shorter overall survival (OS) in AML patients (p = 0.002). Moreover, patients with high expression of PRR34‐AS1 had significantly lower complete remission (CR) rate compared with those with low expression of PRR34‐AS1 after induction chemotherapy. Furthermore, multivariate analysis confirmed that PRR34‐AS1 expression was an independent factor affecting CR in whole‐AML, non‐APL‐AML, and CN‐AML patients (p = 0.032, 0.039, and 0.036, respectively). Methylation‐specific PCR (MSP) and bisulfite sequencing PCR (BSP) were used to explore the methylation status of PRR34‐AS1. PRR34‐AS1 promoter showed a pattern of hypomethylation in AML patients compared with normal controls (p = 0.122). Notably, of whole‐AML and non‐APL‐AML patients, PRR34‐AS1 hypomethylated patients presented a significantly shorter OS than those with a hypermethylated PRR34‐AS1 (p = 0.010 and 0.037, respectively). Multivariate analysis confirmed that the hypomethylation of PRR34‐AS1 served as an independent prognostic indicator in both whole‐cohort AML and non‐APL‐AML categories (p = 0.057 and 0.018, respectively). In summary, the findings of this study showed that abnormalities in PRR34‐AS1 are associated with poor prognosis in AML. Therefore, monitoring this index may be important in the prognosis of AML and can provide information on effective chemotherapy against the disease.

Keywords

• acute myeloid leukemia
• DNA methylation
• expression
• lncRNAs
• prognosis
• PRR34‐AS1