J Cancer 2017; 8(3):460-468. doi:10.7150/jca.16914
Epigenetic dysregulation of NKD2 is a valuable predictor assessing treatment outcome in acute myeloid leukemia
1. Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China;
2. Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
*These authors contributed equally to this work.
Li Xx, Zhou Jd, Zhang Tj, Yang L, Wen Xm, Ma Jc, Yang J, Zhang Zh, Lin J, Qian J. Epigenetic dysregulation of NKD2 is a valuable predictor assessing treatment outcome in acute myeloid leukemia. J Cancer 2017; 8(3):460-468. doi:10.7150/jca.16914. Available from http://www.jcancer.org/v08p0460.htm
AIM: The present study was aimed to investigate NKD2 expression as well as promoter methylation and further analyze their clinical significance in patients with acute myeloid leukemia (AML).
METHODS: Real-time quantitative PCR was carried out to detect the pattern of NKD2 expression in 113 AML patients and 24 controls. Real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP) were carried out to detect NKD2 promoter methylation in 101 AML patients and 24 controls with available DNA.
RESULTS: The level of NKD2 transcript in AML patients was significantly down-regulated as compared with controls (P=0.039). NKD2 methylation level in AML patients was significantly higher than controls (P=0.044). Moreover, NKD2 methylation negatively correlated with NKD2 expression in AML patients (R=-0.218, P=0.029). Furthermore, demethylation of NKD2 could increase NKD2 expression in the leukemic cell line THP1 (P<0.05). NKD2 low-expressed and high-expressed patients showed no statistical significance in complete remission (CR) rate among cytogenetically normal AML (CN-AML). However, low NKD2 expression was associated with shorter overall survival (OS) time and acted as independent risk factor in CN-AML according to Kaplan-Meier (P=0.029) and Cox regression analyses (P=0.022). Furthermore, gene expression (GEP) data also confirmed the prognostic value of NKD2 expression in CN-AML patients. Moreover, NKD2 showed significantly increased level in post-CR than initial diagnosis in follow-up AML patients (P=0.024).
CONCLUSION: Decreased NKD2 expression inactivated by promoter hypermethylation is a common event in AML and is associated with adverse outcome in CN-AML patients.
Keywords: NKD2, expression, methylation, prognosis, acute myeloid leukemia.