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Decreased SCIN expression, associated with promoter methylation, is a valuable predictor for prognosis in acute myeloid leukemia
Author(s) -
Zhang ZhiHui,
Zhang Wei,
Zhou JingDong,
Zhang TingJuan,
Ma JiChun,
Xu ZiJun,
Lian XinYue,
Wu DeHong,
Wen XiangMei,
Deng ZhaoQun,
Lin Jiang,
Qian Jun
Publication year - 2018
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22794
Subject(s) - methylation , myeloid leukemia , biology , cancer research , dna methylation , medicine , gene expression , gene , genetics
The present study was aimed to investigate SCIN expression as well as promoter methylation and further explore their clinical relevance in acute myeloid leukemia (AML) patients. Real‐time quantitative PCR was carried out to detect the expression level of SCIN in 119 AML patients and 37 healthy controls. Real‐time quantitative methylation‐specific PCR and bisulfite sequencing PCR were carried out to detect SCIN promoter methylation levels in 103 AML patients and 29 controls. As compared with controls, the level of SCIN transcript was significantly down‐regulated in AML patients ( P = 0.001), and the level of methylated SCIN promoter was significantly higher in AML patients ( P = 0.001). Moreover, the level of promoter methylation was weakly negatively correlated with SCIN expression in AML patients ( R = −0.265, P = 0.027). Demethylation of SCIN promoter by 5‐aza‐2′‐deoxycytidine could restore its expression in leukemic cell line THP1. The age of SCIN low patients was significantly higher and C/EBPA mutation was significantly less than SCIN high patients ( P = 0.039 and 0.038, respectively). Moreover, the rate of complete remission (CR) of SCIN low patients was significantly lower than SCIN high patients ( P = 0.009). Kaplan‐Meier analysis showed that low SCIN expression was associated with shorter overall survival ( P = 0.036). Cox regression analysis demonstrated low SCIN expression was an independent poor prognostic factor ( P = 0.047). Furthermore, SCIN expression was restored in those patients who achieved CR after induction therapy ( P = 0.003). These findings indicate that decreased SCIN expression associated with its promoter methylation is a valuable biomarker for predicting adverse prognosis in AML patients.