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SCIN 表达降低,与启动子甲基化有关,是急性髓系白血病预后的一个有价值的预测指标。

Decreased SCIN expression, associated with promoter methylation, is a valuable predictor for prognosis in acute myeloid leukemia.

机构信息

Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.

The Key Lab of Precision Diagnosis and Treatment of Zhenjiang City, Zhenjiang, Jiangsu, People's Republic of China.

出版信息

Mol Carcinog. 2018 Jun;57(6):735-744. doi: 10.1002/mc.22794. Epub 2018 Mar 6.

DOI:10.1002/mc.22794
PMID:29457658
Abstract

The present study was aimed to investigate SCIN expression as well as promoter methylation and further explore their clinical relevance in acute myeloid leukemia (AML) patients. Real-time quantitative PCR was carried out to detect the expression level of SCIN in 119 AML patients and 37 healthy controls. Real-time quantitative methylation-specific PCR and bisulfite sequencing PCR were carried out to detect SCIN promoter methylation levels in 103 AML patients and 29 controls. As compared with controls, the level of SCIN transcript was significantly down-regulated in AML patients (P = 0.001), and the level of methylated SCIN promoter was significantly higher in AML patients (P = 0.001). Moreover, the level of promoter methylation was weakly negatively correlated with SCIN expression in AML patients (R = -0.265, P = 0.027). Demethylation of SCIN promoter by 5-aza-2'-deoxycytidine could restore its expression in leukemic cell line THP1. The age of SCIN patients was significantly higher and C/EBPA mutation was significantly less than SCIN patients (P = 0.039 and 0.038, respectively). Moreover, the rate of complete remission (CR) of SCIN patients was significantly lower than SCIN patients (P = 0.009). Kaplan-Meier analysis showed that low SCIN expression was associated with shorter overall survival (P = 0.036). Cox regression analysis demonstrated low SCIN expression was an independent poor prognostic factor (P = 0.047). Furthermore, SCIN expression was restored in those patients who achieved CR after induction therapy (P = 0.003). These findings indicate that decreased SCIN expression associated with its promoter methylation is a valuable biomarker for predicting adverse prognosis in AML patients.

摘要

本研究旨在探讨 SCIN 表达及其启动子甲基化,并进一步探讨其在急性髓系白血病(AML)患者中的临床相关性。采用实时定量 PCR 检测 119 例 AML 患者和 37 例健康对照者的 SCIN 表达水平。采用实时定量甲基化特异性 PCR 和亚硫酸氢盐测序 PCR 检测 103 例 AML 患者和 29 例对照者的 SCIN 启动子甲基化水平。与对照组相比,AML 患者的 SCIN 转录本水平显著下调(P=0.001),AML 患者的 SCIN 启动子甲基化水平显著升高(P=0.001)。此外,AML 患者中启动子甲基化水平与 SCIN 表达呈弱负相关(R=-0.265,P=0.027)。5-氮杂-2'-脱氧胞苷去甲基化可恢复白血病细胞系 THP1 中 SCIN 的表达。SCIN 患者的年龄明显较高,C/EBPA 突变明显少于 SCIN 患者(P=0.039 和 0.038)。此外,SCIN 患者的完全缓解(CR)率明显低于 SCIN 患者(P=0.009)。Kaplan-Meier 分析显示,低 SCIN 表达与总生存期较短相关(P=0.036)。Cox 回归分析表明,低 SCIN 表达是独立的不良预后因素(P=0.047)。此外,那些在诱导治疗后达到 CR 的患者中 SCIN 表达得到恢复(P=0.003)。这些发现表明,SCIN 表达降低与其启动子甲基化相关,是预测 AML 患者不良预后的有价值的生物标志物。

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