Hypomethylation of let-7a-3 is associated with poor prognosis in myelodysplastic syndrome

Abstract

Abnormal methylation of let-7a-3 has been found in various cancers and may consequently affect their survival. In this study, real-time quantitative methylation specific PCR (RQ-MSP) was used to determine the unmethylation level of let-7a-3 in 95 patients with myelodysplastic syndrome (MDS). The hypomethylation of let-7a-3 promoter was detected in 22 of 95 (23.2%) patients with MDS compared to 4.2% (1/24) of controls (p= 0.0419). Moreover, the frequency of let-7a-3 hypomethylation was higher in older patients (≥70 years) than in younger patients (<70 years). No significant difference was observed in distribution of WHO, IPSS, and cytogenetic classification. However, hypomethylated patients had significantly shorter overall survival than those without hypomethylation (p= 0.007). Moreover both Kaplan–Meier and Multivariate Cox analyses confirmed that let-7a-3 hypomethylation was an independent prognostic risk factor in cohorts of MDS patients with lower-risk disease. Our study suggested that let-7a-3 hypomethylation may predict poor outcome in MDS.

Keywords:

• Hypomethylation
• let-7a-3
• myelodysplastic syndrome
• prognosis

Acknowledgments

This work was supported by National Natural Science foundation of China [81270630, 81172592], Six major talent summit project in Jiangsu Province [WSN-112], Science and Technology Special Project in Clinical Medicine of Jiangsu Province [BL2012056], Social Development Foundation of Zhenjiang [SH2014044,SH2014086], Research and Development Foundation of Clinical Medicine of Jiangsu University [JLY20140018].

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1187273.