ABSTRACT
Objective:To investigate the role of methylation status of glutathione transferase mu5 (GSTM5) promoter region in the occurrence and development of myelodysplastic syndrome (MDS) and provide a new potential molecular marker for the early diagnosis of MDS.Method:Bone marrow blood samples were collected from 40 patients with initial diagnosis of MDS [5 cases of MDS with single dysplasia (MDS-SLD), 7 cases of MDS with multilineage dysplasia (MDS-MLD), 6 cases of MDS with ringed sideroblasts (MDS-RS), 13 patients with refractory with excess blast-1 (RAEB1), 9 patients with refractory with excess blast-2 (RAEB2)], 8 patients with AML secondary to MDS and 6 patients with non-malignant blood diseases(4 patients with iron deficiency anemia and 2 patients with nutritional megaloblastic anemia) in PLA General Hospital from October 2018 to June 2021. Methylation status of the promoter region of GSTM5 gene in three groups were detected by the Agena MassArray nucleic acid mass spectrometry. The Wilcoxon nonparametric test (non-normally distributed data, median (IQR)] was used to compare the methylation levels of GSTM5 gene in different groups. Receiver operating characteristic (ROC) curve was used to evaluate the specificity, sensitivity and accuracy of the test.Results:Cluster analysis showed that the methylation status of GSTM5 in MDS group was higher than that in control group [0.50 (0.27, 0.79) vs.0.29(0.10, 0.45), P<0.05]; The methylation status of GSTM5 in sAML group was significantly higher than that in MDS group [0.67 (0.36, 0.86) vs. 0.50 (0.27, 0.79), P<0.05].The differences in the methylation status of each CpG site were analyzed, and there were statistically significant differences between the MDS group and the control group at CpG_1, CpG_4, 5, CpG_6, 7, 8, CpG_11, CpG_13, 14, CpG_15, CpG_16, CpG_22 and CpG_24 sites ( P<0.05). The results of ROC curve analysis showed that the area under the CpG_6, 7, 8 site curves was the largest, with AUC=0.861(95% CI 0.717-1.000; P<0.05), and the sensitivity and specificity were 85% and 83%, respectively. By analyzing the relationship between GSTM5 methylation and MDS disease development, GSTM5 methylation levels were significantly increased in the higher bone marrow blast group and the high-risk subgroup (RAEB). Conclusion:Aberrant DNA promoter methylation of GSTM5 was a frequent event in MDS and may play an important role in the occurrence and development of MDS. It might be served as a promising biomarker in the diagnosis of MDS.