多基因甲基化在骨髓增生异常综合征患者中的预后价值

摘要

Objective:To analyze the methylation status of p15,DAPK,SOCS1 and FHIT genes in patients with myelodysplastic syndrome (MDS) and to explore the prognostic significance of gene methylation.Methods:Methylation-specific PCR (MSP) was used to detect the methylation of the above-mentioned 4 genes in 67 patients with MDS and 18 patients with iron-deficient anemia as controls.The gene methylation status of MDS patients and its effect on prognosis were analyzed.Results:The methylation rates of p15,DAPK,SOCS1 and FHIT in 67 MDS patients were 37.3％,35.8％,47.8％ and 52.2％,respectively,which were significantly higher than those in the control group (P ≤ 0.05).The methylation status of p15,SOCS1 was increased along with the increase of International Prognostic Scoring System(IPSS) scores (P ≤0.05),ands≥2 genes was more frequent in relatively high risk groups (P ≤0.05).The median overall survival time of patients with and without methylation were 15 and 21 months,respectively (P ≤ 0.05).Patients showing methylation of SOCS1 had a significantly shorter survival time in relatively low risk groups(P ≤ 0.05),meanwhile SOCS1,p15 and methylations of ≥2 genes had significantly shorter survival time in relatively high risk groups(P ≤ 0.05).In multivariate analysis,SOCS1 and p15 were negative prognostic factors.Conclusion:p15,DAPK,SOCS1 and FHIT are higher hypermethylated genes in MDS.The methylations of SOCS1 and p15 are independent prognostic factor for overall survival in MDS.%目的:分析p15、DAPK、SOCS1和FHIT基因在骨髓增生异常综合征(MDS)患者中的甲基化状况,探讨基因甲基化在MDS中的预后价值.方法:应用甲基化特异性PCR (MSP)对67例MDS患者骨髓进行上述4种基因甲基化的检测,选择18例缺铁性贫血患者作为对照,分析MDS患者基因甲基化状况及其对生存率的影响.结果:67例MDS患者中p15、DAPK、SOCS1和FHIT4种基因甲基化率分别为37.3％、35.8％、47.8％和52.2％,较对照组显著增高(P≤0.05);随着国际预后积分系统(IPSS)评分的增加,p15、SOCS1基因甲基化率呈增高趋势(P≤0.05),同时表达≥2个基因甲基化更易见于相对高危组患者(P≤0.05).生存分析显示,有基因甲基化和无基因甲基化患者的中位生存时间分别为15和21个月(P≤0.05),在相对低危组中SCOS1基因甲基化患者生存时间短于非甲基化患者(P≤0.05),在相对高危组中SOCS1、p15及≥2个基因甲基化患者生存时间明显短于非甲基化患者(P≤0.05).多因素分析显示,SOCS1及p15基因甲基化是MDS患者预后不良的影响因素.结论:p15、DAPK、SOCS1和FHIT是MDS中出现较高的甲基化基因,SOCS1及p15基因甲基化是MDS患者不良预后的独立危险因素.