SPAG6在骨髓增生异常综合征患者中的表达及其基因启动子甲基化状态

Expression level of sperm-associated antigen 6 and its gene promoter methylation status in myelodysplastic syndrome patients

目的探讨SPAG6在骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者中的表达水平与临床参数相关性以及基因启动子甲基化状态对SPAG6转录调控的影响。方法采用RT-qPCR及Western blot检测18例MDS及MDS-AML患者和20例健康对照者骨髓细胞SPAG6表达水平;甲基化特异性PCR(MS-PCR)法检测MDS患者和对照组(包括初诊缺铁性贫血患者和健康体检人群)SPAG6启动子甲基化状态;分析SPAG6启动子甲基化状态及表达水平与患者临床参数相关性。结果与健康对照组比较,MDS患者SPAG6表达水平明显升高,且SPAG6启动子区域呈现异常低甲基化(P<0.01)。SPAG6表达水平与患者年龄、骨髓原始细胞比例、危险分层有相关性(P<0.05),与患者性别无相关性(P>0.05)。SPAG6基因启动子异常低甲基化状态与患者年龄、疾病危险分层有相关性(P<0.05),与患者性别、骨髓原始细胞比例无相关性(P>0.05)。结论 SPAG6在MDS患者中高表达,并且与疾病发生、进展以及不良预后相关,表观遗传调控可能是SPAG6转录调控的重要机制之一。

Objective To investigate the association between sperm-associated antigen 6(SPAG6)expression level and the clinical parameters of patients with myelodysplastic syndrome(MDS)and explore how SPAG6 gene promoter methylation status regulates SPAG6 transcription.Methods Bone marrow mononuclear cells(BMMNCs)were collected from 18 patients with MDS or MDS-acute myeloid leukemia(MDS-AML)and20 healthy control subjects for detection of SPAG6 expression using RT-qPCR and Western blotting.The methylation status of SPAG6 promoter in patients with MDS and the healthy controls was assessed using methylation-specific PCR(MS-PCR).The correlation of SPAG6 promoter methylation status and SPAG6 expression level with the clinical parameters of patients were analyzed.Results Compared with the healthy control subjects,the patients with MDS showed significantly increased expression levels of SPAG6 in the BMMNCs with significant abnormal hypomethylation in SPAG6 gene promoter region(P<0.01).In the patients with MDS,the expression level of SPAG6 in the BMMNCs was significantly correlated with the patients’age,bone marrow blast cell ratio and risk stratification(P<0.05)but not with the patients’gender(P>0.05).The abnormal hypomethylation of SPAG6 gene promoter was significantly correlated with age and disease risk stratification(P<0.05)but not with gender or bone marrow blast cell ratio(P>0.05).Conclusion SPAG6 is highly expressed in the BMMNCs of patients with MDS,which is associated with the occurrence,progression and a poor prognosis of the disease.Epigenetic regulation can be an important mechanism for transcriptional regulation of SPAG6.