Hypermethylation of secreted frizzled-related proteins predicts poor prognosis in non-M3 acute myeloid leukemia

作者：Hong Guo, Ting‐juan Zhang, Xiang‐mei Wen, Jing‐dong Zhou, Ji‐chun Ma, An Cui, Wei Zhang, Zi‐jun Xu, Jiang Lin, Jun Qian · 发表于：OncoTargets and Therapy · 年份：2017 · DOI：10.2147/ott.s136502 · 被引用次数：12 · 研究领域：Wnt/β-catenin signaling in development and cancer、Epigenetics and DNA Methylation、Acute Myeloid Leukemia Research

Objective: 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. Methods: SFRPs methylation in 139 primary non-M3 AML patients was determined using methylation-specific real-time quantitative polymerase chain reaction. Results: 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 ...