SOX7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 Methylation Status of SOX7 in Patients with Myelodysplastic Syndrome

目的探讨SRY7蛋白(sex determining region Y-box 7,SOX7)基因甲基化在骨髓增生异常综合征(myelodysplatic syndrome,MDS)中的预后价值。方法通过5-氮杂-2-脱氧胞苷(5-aza-2’-dC)处理及甲基化特异性逆转录-聚合酶链反应(MSP)发现细胞株(TPH-1和SKM-1)存在SOX7基因甲基化,再以161例MDS患者骨髓样本检测SOX7基因甲基化状态,评价其对预后的影响。结果 SOX7基因甲基化存在于THP-1和SKM-1细胞株中,并在5-aza-2’-dC处理后表达上调。59.6%(96/161)MDS患者存在SOX7基因甲基化,而6例正常人无SOX7甲基化。SOX7甲基化阳性率在MDS不同的世界卫生组织(World Health Organization,WHO)亚型中存在差异,有统计学意义(P=0.005);同时随着国际预后积分系统(international prognostic scoring system,IPSS)积分的增加,该甲基化阳性率呈上升趋势,差异有统计学意义(P<0.001)。生存分析提示,SOX7甲基化阳性患者与甲基化阴性患者相比,整体生存时间(overall survival,OS)明显缩短:甲基化阳性者中位生存时间为18.5个月,而甲基化阴性患者的中位生存时间为31.8个月,差异有统计学意义(P=0.012),但对白血病生存(leukemia free survival,LFS)时间无明显影响(P=0.056)。结论SOX7基因甲基化与MDS患者的OS相关,在MDS患者的发病和发展中起了重要作用。

Objective To investigate the aberrant methylation and the prognostic significance of sex-determining region Y-box 7 gene promoter in patients with myelodysplastic syndrome （MDS）. Methods SOX7 methylation was also detected in leukemia cell lines （THP-1 and SKM-1） treated with 5-aza-2＇ deoxycytidine （5-aza-2＇-dC） and Methylation-specific PCR （MSP）. The bone marrow samples of 161 MDS patient were collected from 8 hospitals of Shanghai. determine The prognostic value in patients with MDS was evaluated. Results SOX7 methylation was detected in leukemia cell lines （THP1 and SKM-1 ）, and the mRNA levelsof SOX7 were up-regulated after treated with 5-aza-2-deoxycytidine （5-aza-2＇- dC）. SOX7 methylation was detected in 59. 6% （96/191） patients, and no hypermathylation was observed in 6 normal samples. A significantly higher frequency of SOX7 methylation appeared in patients with advanced stages of World Health Organization （WHO） subtypes （P = 0. 005） and the positive rate was increased along with the increase of International Prognostic Scoring System （IPSS） scores （P〈0. 001）. Though SOX7 methylation did not correlate with risk of transformation to acute myeloid leukemia （AML） （P = 0. 056）, patients with SOX7 methylation had shorter survival time （P = 0. 012）. The median survival time of patients with SOX7 methylation were 18.5 months, which was significant different with that of the patients without methylation （31.8 months）. Conclusion The methylation status of SOX7 is related with the overall survival of the MDS patients,and plays a important role in the occurrence and development of MDS.