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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 gene in patients with myelodysplastic syndrome (MDS) and explore the prognostic value of gene methylation in MDS. Methods: Methylation-specific PCR (MSP) was used to detect the methylation of the four genes in the bone marrow of 67 patients with MDS. 18 patients with iron deficiency anemia were selected as control, and the methylation status of MDS patients was analyzed Impact on survival. Results: The methylation rates of p15, DAPK, SOCS1 and FHIT in 67 M DS patients were 37.3%, 35.8%, 47.8% and 52.2%, respectively, which were significantly higher than those in control group (P <0.05) Prognostic score system (IPSS) score increased, p15, SOCS1 gene methylation increased (P <0.05), while the expression of more than two genes methylation was more common in patients with relatively high risk group (P <0.05). Survival analysis showed that the median survival time of patients with gene methylation and gene-free methylation were 15 and 21 months respectively (P <0.05), and the survival time of SCOS1 methylation patients in the relatively low-risk group was shorter than In non-methylation patients (P <0.05), the survival time of SOCS1, p15 and ≥2 methylation patients in the relatively high-risk group was significantly shorter than that in non-methylation patients (P <0.05). Multivariate analysis showed that methylation of SOCS1 and p15 genes were the influencing factors of poor prognosis in patients with MDS. Conclusion: p15, DAPK, SOCS1 and FHIT are the higher methylated genes in M DS and the methylation of SOCS1 and p15 genes are independent risk factors for poor prognosis in M DS patients.