SOX7 methylation is an independent prognostic factor in myelodysplastic syndromes.

OBJECTIVE:SOX7 downregulation caused by its promoter methylation was associated with poor survival in several types of human solid tumors. However, the pattern of SOX7 methylation and its clinical significance are less studied in hematological malignancies. Herein, we evaluated the methylation pattern of SOX7 in myelodysplastic syndrome (MDS) and determined its clinical implication in patients with MDS. METHODS:SOX7 methylation was determined by real-time quantitative methylation-specific PCR in 99 MDS patients. Bisulfite sequencing PCR was applied to confirm the results of methylation was detected in 55.6% of 99 patients but not in healthy donors. No correlation was found between SOX7 methylation and clinical parameters including patient age, gender, white blood cell count, hemoglobin, and platelet count. However, patients with SOX7 methylation harbored more U2AF1 mutation than patients without SOX7 methylation (P = 0.015). Kaplan-Meier curves indicated that the patients with SOX7 methylation presented reduced overall survival (OS) (P =  0.034). Furthermore, subgroup analysis indicated that SOX7 methylation was associated with poor OS in male patients (P = 0.034) and in patients older than 60 years (P = 0.019). According to the multivariate analysis, SOX7 methylation remained as an independent prognosis factor in MDS patients both as dichotomous (HR = 2.14, P =  0.041) and as continuous (HR = 1.55, P =  0.042) variable. Importantly, SOX7 methylation was significantly increased during progression from MDS to secondary acute myeloid leukemia (sAML). CONCLUSIONS:Our findings demonstrated that SOX7 methylation conferred adverse prognosis in MDS patients and was associated with leukemia progression.

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