A 3-miRNA signature predicts prognosis of pediatric and adolescent cytogenetically normal acute myeloid leukemia
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Ruiqi Zhu1, Weiwei Zhao2, Fengjuan Fan1, Liang Tang1, Jingdi Liu1, Ting Luo1, Jun Deng1, Yu Hu1
1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
2Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin, 150086, China
Yu Hu, email: [email protected]
Liang Tang, email: [email protected]
Keywords: pediatric and adolescent, CN-AML, miRNA, signature, prognosis
Received: January 02, 2017 Accepted: April 04, 2017 Published: April 17, 2017
Acute myeloid leukemia is a hematologic malignancy with significant molecular heterogeneity. MicroRNAs have important biological functions and play critical roles in pathogenesis and prognosis in a variety of cancers including acute myeloid leukemia. Some reports have constructed risk stratification systems for adult acute myeloid leukemia patients using microRNAs to predict an optimal outcome of patients. However, little has been done in pediatric and adolescent patients. The purpose of this study is to identify a panel of microRNA signature that could predict prognosis in younger cytogenetically normal acute myeloid leukemia patients by analyzing the data from The Cancer Genome Atlas. A total of 59 cytogenetically normal acute myeloid leukemia patients under 21 years with corresponding clinical data were enrolled in our study. Using univariate Cox’s model, we found 17 miRNAs were significantly related with overall survival in pediatric and adolescent cytogenetically normal acute myeloid leukemia patients but no clinical parameter was found significant related with overall survival. The multivariate Cox regression identified high expression of hsa-miR-146b was independent poor prognostic factor and high expression of hsa-miR-181c and hsa-miR-4786 appeared to be favorable factors. A model was proposed based on these three miRNAs. Leave-one-out Cross Validation method and Permutation Test was further used to evaluate this model. The function role of has-mir-181c was further studied by carrying out flow cytometry and cell counting kit-8 (CCK-8) in U937 cell line. The results indicate that the 3-microRNA-based signature is a reliable prognostic biomarker for pediatric and adolescent cytogenetically normal acute myeloid leukemia patients.
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