Prognostic Value of Multigene Methylation in Patients with Myelodysplastic Syndrome

OBJECTIVE: To analyze the methylation status of p15, DAPK, SOCS1 and FHIT genes in patients with myelodysplastic syndrome(MDS) and to explore the prognostic significance of gene methylation. METHODS: Methylation-specific PCR (MSP) was used to detect the methylation of the above-mentioned 4 genes in 67 patients with MDS and 18 patients with iron-deficient anemia as controls. The gene methylation status of MDS patients and its effect on prognosis were analyzed. RESULTS: The methylation rates of p15, DAPK, SOCS1 and FHIT in 67 MDS patients were 37.3%, 35.8%, 47.8% and 52.2%, respectively, which were significantly higher than those in the control group (P<0.05). The methylation status of p15, SOCS1 was increased along with the increase of International Prognostic Scoring System(IPSS) scores (P<0.05), and ≥2 genes was more frequent in relatively high risk groups (P<0.05). The median overall survival time of patients with and without methylation were 15 and 21 months, respectively (P<0.05). Patients showing methylation of SOCS1 had a significantly shorter survival time in relatively low risk groups(P<0.05), meanwhile SOCS1, p15 and methylations of ≥2 genes had significantly shorter survival time in relatively high risk groups(P<0.05). In multivariate analysis, SOCS1 and p15 were negative prognostic factors. CONCLUSION: p15, DAPK, SOCS1 and FHIT are higher hypermethylated genes in MDS. The methylations of SOCS1 and p15 are independent prognostic factor for overall survival in MDS.