title: 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.
authors.affiliation: a Department of Hematology , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.|c Department of Hematology , the Third People's Hospital of Kunshan City , Kunshan , China.
authors.forename: De-Hong
authors.initials: DH
authors.lastname: Wu
authors.affiliation: b Laboratory Center , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Yao
authors.affiliation: a Department of Hematology , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: b Laboratory Center , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Ji-Chun
authors.initials: JC
authors.lastname: Ma
authors.affiliation: b Laboratory Center , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Wen
authors.affiliation: a Department of Hematology , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: b Laboratory Center , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: a Department of Hematology , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Xi-Xi
authors.initials: XX
authors.lastname: Li
authors.affiliation: b Laboratory Center , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.affiliation: b Laboratory Center , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.affiliation: a Department of Hematology , Affiliated People's Hospital of Jiangsu University , Zhenjiang , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: Hypomethylation; let-7a-3; myelodysplastic syndrome; prognosis