Abnormal Methylation of the Sex-Determining Region Y-box 17 (SOX17) Promoter Predicts Poor Prognosis in Myelodysplastic Syndrome
Abnormal Methylation of the Sex-Determining Region Y-box 17 (SOX17) Promoter Predicts Poor Prognosis in Myelodysplastic Syndrome
复制标题
性别决定区 Y-box 17 (SOX17) 启动子的异常甲基化预示着骨髓增生异常综合征的不良预后。
DOI：
10.7754/clin.lab.2013.130414
复制
发表时间：
2014-01-01
影响因子：
0.7
通讯作者：
Lin, Guo-Wei
中科院分区：
文献类型：
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作者：
Fan, Rong;Zhao, Xiao-Li;Lin, Guo-Wei
背景
性别决定区 Y-box 17 (SOX17) 是高迁移率族 (HMG) 转录因子家族的成员，在发育和干/前体细胞功能的调节中发挥着关键作用。最近的证据表明，SOX17 可以作为肿瘤抑制基因，至少部分通过抑制 Wnt 通路活性来发挥作用。
方法
在这里，我们报告在 THP-1 和 SKM-I 细胞系中检测到 SOX17 甲基化，并且 5-aza-dC 上调 SOX17 mRNA 水平。为了阐明 SOXI7 在 MDS 中的作用，采用甲基化特异性 PCR (MSP) 检测 164 例成人新发 MDS 患者和 6 例正常样本中 SOX17 的甲基化状态。
结果
我们发现 58.5% (n = 96) 的这些患者中存在 SOX17 甲基化，而正常样本中则没有。甲基化与世界卫生组织（WHO）亚型和国际预后评分系统（IPSS）风险组显着相关。 WHO 亚型晚期患者（69.6% vs. 44.4%，p = 0.001）和较高风险 IPSS 亚组（69.8% vs. 48.8%，p = 0.010）的 SOX17 甲基化频率显着较高。尽管多变量分析表明 SOX17 甲基化状态不是影响总生存期 (OS) 的独立因素 (HR = 0.097)，但有和没有 SOX17 甲基化的患者之间的骨髓原始细胞水平和 IPSS 风险亚组存在显着差异。
结论
这些发现表明 SOX17 启动子的高甲基化可能是 MDS 发展的早期事件之一，并预示着不良预后。
BACKGROUND
The sex-determining region Y-box 17 (SOX17) is a member of the high mobility group (HMG) transcription factor family, which plays critical roles in the regulation of development and stem/precursor cell function. Recent evidence demonstrated that SOX17 acts as a tumor-suppressor gene, at least partly though repression of Wnt pathway activity.
METHODS
Here we report that SOX17 methylation was detected in THP-1 and SKM-I cell lines and SOX17 mRNA levels was up-regulated by 5-aza-dC. To clarify the role of SOXI7 in MDS, methylation-specific PCR (MSP) was employed to examine the methylation status of SOX17 in 164 adult de novo MDS patients and 6 normal samples.
RESULTS
We found that SOX17 methylation was presented in 58.5% (n = 96) of these patients and none of the normal samples. Methylation was correlated significantly with World Health Organization (WHO) subtypes and international prognostic scoring system (IPSS) risk group. Patients with advanced stages of WHO subtypes (69.6% vs. 44.4%, p = 0.001) and higher risk IPSS subgroups (69.8% vs. 48.8%, p = 0.010) exhibited a significantly higher frequency of SOX17 methylation. Though multivariate analysis indicated that SOX17 methylation status was not the independent factor that impacted overall survival (OS) (HR = 0.097), there were significant differences in marrow blast levels and the IPSS risk subgroups between patients with and without SOX17 methylation.
CONCLUSIONS
These findings suggest that the hypermethylation of SOX17 promoter may be one of the early events in the development of MDS and predicts poor prognosis.