Liu Xiaoliu, Liu Sufang, Lei Jian, Zou Lixin, Xiao Le, Zhang Guangsen
Department of Hematology, The Affiliated Changsha Hospital, Hunan Normal University, Changsha, Hunan 410006, P.R. China.
Division of Hematology, Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
Exp Ther Med. 2018 Jan;15(1):500-505. doi: 10.3892/etm.2017.5402. Epub 2017 Oct 30.
As a highly heterogeneous disease, the pathogenesis of myelodysplastic syndrome (MDS) has not been well defined. In the present study, human mutS homolog 2 (hMSH2) promoter methylation was detected with methylation-specific polymerase chain reaction (PCR). The function of hMSH2 was analyzed by microsatellite instability (MSI) detection of BAT-26, and hMSH2 expression was evaluated using reverse transcription-quantitative PCR in 60 patients with MDS. The results revealed methylation of the hMSH2 promoter in 18 patients with MDS who have an overall prevalence of 30% (95% confidence interval, 18.4-41.6%). Among the patients with hMSH2 methylation, 2 patients exhibited MSI. It was demonstrated that hMSH2 promoter methylation was increased in MDS with an increase in Revised International Prognostic Scoring System (IPSS-R) risk, and patients with higher hMSH2 promoter methylation had shorter overall survival by Kaplan-Meier analysis (P=0.011). In addition, it was also observed that decreased hMSH2 mRNA expression was associated with high IPSS-R risk group (high/very high vs. intermediate, P=0.003), and hMSH2 mRNA expression in CD34 positive bone marrow cells was lower compared with that in CD34 negative cells of patients with MDS (P=0.029). Methylation of hMSH2 may be valuable for prognostic evaluation and progression prediction of MDS. Furthermore, hMSH2 may serve a key function in the pathogenesis and prognosis of MDS.
作为一种高度异质性疾病，骨髓增生异常综合征（MDS）的发病机制尚未完全明确。在本研究中，采用甲基化特异性聚合酶链反应（PCR）检测人错配修复蛋白2（hMSH2）启动子甲基化。通过检测BAT-26的微卫星不稳定性（MSI）分析hMSH2的功能，并运用逆转录定量PCR评估60例MDS患者的hMSH2表达。结果显示，18例MDS患者存在hMSH2启动子甲基化，总体发生率为30%（95%置信区间，18.4 - 41.6%）。在hMSH2甲基化的患者中，有2例表现出MSI。结果表明，随着修订的国际预后评分系统（IPSS-R）风险增加，MDS患者中hMSH2启动子甲基化水平升高，通过Kaplan-Meier分析发现，hMSH2启动子甲基化水平较高的患者总生存期较短（P = 0.011）。此外，还观察到hMSH2 mRNA表达降低与高IPSS-R风险组相关（高/极高风险组与中危组相比，P = 0.003），且MDS患者CD34阳性骨髓细胞中的hMSH2 mRNA表达低于CD34阴性细胞（P = 0.029）。hMSH2甲基化可能对MDS的预后评估和病情进展预测具有重要价值。此外，hMSH2可能在MDS的发病机制和预后中发挥关键作用。
