Zhou Jing-Dong, Lin Jiang, Zhang Ting-Juan, Ma Ji-Chun, Yang Lei, Wen Xiang-Mei, Guo Hong, Yang Jing, Deng Zhao-Qun, Qian Jun
Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Cancer Med. 2017 Jan;6(1):267-274. doi: 10.1002/cam4.984. Epub 2016 Nov 28.
Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome (MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia (AML) patients (P = 0.024 and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A mutation (P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly shorter overall survival (OS) time than those with GPX3 unmethylation analyzed with Kaplan-Meier analysis (P = 0.012). Moreover, Cox regression analysis revealed that GPX3 methylation might act as an independent prognostic indicator in MDS (HR = 1.847, P = 0.072). GPX3 methylation density was significantly increased during the progression from MDS to secondary acute myeloid leukemia (sAML) in three follow-up paired patients. Our study concludes that GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in MDS.
在包括白血病在内的多种癌症中，已发现GPX3的表观遗传失活。此外，异常DNA甲基化也被发现是骨髓增生异常综合征（MDS）疾病进展的主要机制。本研究旨在探讨110例MDS患者中GPX3启动子甲基化及其临床相关性。通过实时定量甲基化特异性PCR（RQ-MSP）和亚硫酸氢盐测序PCR（BSP）检测GPX3甲基化。在15%（17/110）的MDS患者中发现了GPX3甲基化，显著高于对照组，低于急性髓系白血病（AML）患者（P = 0.024和0.041）。GPX3甲基化患者年龄较大，DNMT3A突变频率较高（P = 0.015和0.066）。采用Kaplan-Meier分析，GPX3甲基化的病例总生存（OS）时间明显短于GPX3未甲基化的病例（P = 0.012）。此外，Cox回归分析显示，GPX3甲基化可能是MDS的独立预后指标（HR = 1.847，P = 0.072）。在3例随访配对患者中，从MDS进展为继发性急性髓系白血病（sAML）期间，GPX3甲基化密度显著增加。我们的研究得出结论，骨髓中的GPX3甲基化与MDS的不良预后和白血病转化相关。
