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

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.

SUBMITTER: Zhang H

PROVIDER: S-EPMC6444823 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Zhang Huihui H Zhang Ninghan N Wang Rong R Shao Tingting T Feng Yuan Y Yao Yao Y Wu Qingyun Q Zhu Shengyun S Cao Jiang J Zhang Huanxin H Li Zhenyu Z Liu Xuejiao X Niu Mingshan M Xu Kailin K

Journal of translational medicine 20190401 1

<h4>Background</h4>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.<h4>Methods</h4>In this study, we identify miRNAs that could predict clinical outcome in a heterogeneous AML population using TCGA dataset.<h4>Results</h4>We found that MiR-363 is a novel prognostic factor in AML patients undergoing chemotherapy. In multivariable analyses, high miR-363 remained ...[more]

PMID: 30935386

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Project description:Secreted frizzled-related proteins (SFRPs) as Wnt signaling antagonists have been found to be dysregulated by promoter hypermethylation in several cancers including acute myeloid leukemia (AML). This study aimed to investigate the methylated status of SFRPs promoter region and its clinical relevance in Chinese non-M3 AML patients.SFRPs methylation in 139 primary non-M3 AML patients was determined using methylation-specific real-time quantitative polymerase chain reaction.The frequency of aberrant methylation was as follows: 30.2% for SFRP1, 27.3% for SFRP2, 5.0% for SFRP4, and 1.4% for SFRP5. Hypermethylation of at least one SFRP gene occurred in 51.8% (72/139) of non-M3 AML patient samples, which was significantly higher compared to normal control (0/21) (P<0.001). Hypermethylation of SFRP1 was potentially associated with N/K-RAS mutations (P=0.043), and the frequency of SFRPs methylation was higher in patients ≥50 years compared to those <50 years, especially for SFRP2 (P<0.05). Furthermore, both whole cohort and cytogenetically normal (CN) patients with high SFRPs-methylated group showed a shorter overall survival (OS) compared to those with low group (P=0.036 and P=0.035, respectively). Moreover, Cox regression multivariate analysis revealed that SFRPs hypermethylation acts as an independent prognostic biomarker among both whole cohort (hazard ratio =1.804, P=0.026) and CN (hazard ratio =2.477, P=0.023) patients. In leukemic cell line HL60 treated with 5-aza-2'-deoxycytidine, the alteration of SFRP1/2 expression inversely correlated with change in SFRP1/2 methylation (r=-0.975, P=0.005 and r=-0.975, P=0.005, respectively). A tendency of negative correlation was observed between SFRP1 expression and its promoter methylation in AML patients (r=-0.334, P=0.038).These findings suggested that hypermethylation of SFRP1/2 was a frequent event and silenced SFRP1/2 expression in AML. Moreover, hypermethylation of SFRPs promoter was an adverse risk factor for OS in Chinese non-M3 AML patients.

Dataset Information

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

Publications

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

Similar Datasets

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