多基因甲基化在骨髓增生异常综合征患者中的预后价值  

Prognostic Value of Multigene Methylation in Patients with Myelodysplastic Syndrome

作　　者：邓春阳[1] 陈双[1] 江明[1] 尼罗帕尔.吐尔逊 王欢[1] 郝建萍[1] 

机构地区：[1]新疆医科大学第一附属医院血液病中心,新疆乌鲁木齐830054

出　　处：《中国实验血液学杂志》2017年第4期1118-1122,共5页Journal of Experimental Hematology

基　　金：基金项目:新疆维吾尔自治区自然科学基因(2015211C046)

摘　　要：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M DS患者中p15、DAPK、SOCS1和FHIT 4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M DS中出现较高的甲基化基因,SOCS1及p15基因甲基化是M DS患者不良预后的独立危险因素。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 were37. 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）,and ≥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.

关 键 词：骨髓增生异常综合征 DNA甲基化 多基因甲基化 预后价值 

分 类 号：R551.3[医药卫生—血液循环系统疾病]