Circulating miR-150 and miR-342 in plasma are novel potential biomarkers for acute myeloid leukemia

被引:128
|
作者
Fayyad-Kazan, Hussein [1 ]
Bitar, Nizar [2 ]
Najar, Mehdi [3 ]
Lewalle, Philippe [1 ]
Fayyad-Kazan, Mohammad [4 ]
Badran, Rabih [5 ]
Hamade, Eva [2 ]
Daher, Ahmad [2 ]
Hussein, Nader [2 ]
ElDirani, Rim [2 ]
Berri, Fadwa [2 ]
Vanhamme, Luc [6 ,7 ]
Burny, Arsene [1 ]
Martiat, Philippe [1 ]
Rouas, Redouane [1 ]
Badran, Bassam [2 ]
机构
[1] Univ Libre Bruxelles, Inst Jules Bordet, Lab Expt Hematol, B-1000 Brussels, Belgium
[2] Lebanese Univ, Fac Sci, Immunol Lab, Dept Biochem,EDST PRASE, Hadath Beirut, Lebanon
[3] Univ Libre Bruxelles, Hop Erasme, Lab Clin Cell Therapy LTCC, B-1070 Brussels, Belgium
[4] Univ Libre Bruxelles, IBMM, Lab Membrane Transport Biol, B-6041 Gosselies, Belgium
[5] Univ Libre Bruxelles, Dept Math, B-1050 Brussels, Belgium
[6] Univ Libre Bruxelles, IBMM, Mol Parasitol Lab, B-6041 Gosselies, Belgium
[7] Univ Libre Bruxelles, IBMM, Lab Mol Biol Ectoparasites, B-6041 Gosselies, Belgium
来源
关键词
AML; Micro-RNA; Plasma; Biomarker; DOWN-REGULATION; MICRORNAS; CANCER; MARKER; SERUM; EXOSOMES; PCR; CLASSIFICATION; ABNORMALITIES; ACCUMULATION;
D O I
10.1186/1479-5876-11-31
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: MicroRNAs (miRNAs) are small (19-22-nt) single-stranded noncoding RNA molecules whose deregulation of expression can contribute to human disease including the multistep processes of carcinogenesis in human. Circulating miRNAs are emerging biomarkers in many diseases and cancers such as type 2 diabetes, pulmonary disease, colorectal cancer, and gastric cancer among others; however, defining a plasma miRNA signature in acute myeloblastic leukemia (AML) that could serve as a biomarker for diagnosis or in the follow-up has not been done yet. Methods: TaqMan miRNA microarray was performed to identify deregulated miRNAs in the plasma of AML patients. Quantitative real-time RT-PCR was used to validate the results. Receiver-operator characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of the highly and significantly identified deregulated miRNA(s) as potential candidate biomarker(s). Results: The plasma expression level of let-7d, miR-150, miR-339, and miR-342 was down-regulated whilst that of let-7b, and miR-523 was up-regulated in the AML group at diagnosis compared to healthy controls. ROC curve analyses revealed an AUC (the areas under the ROC curve) of 0.835 (95% CI: 0.7119-0.9581; P<0.0001) and 0.8125 (95% CI: 0.6796-0.9454; P=0.0005) for miR-150, and miR-342 respectively. Combined ROC analyses using these 2 miRNAs revealed an elevated AUC of 0.86 (95% CI: 0.7819-0.94; P<0.0001) indicating the additive effect in the diagnostic value of these 2 miRNAs. QRT-PCR results showed that the expression level of these two miRs in complete remission AML patients resembled that of healthy controls. Conclusions: Our findings indicated that plasma miR-150 and miR-342 are novel important promising biomarkers in the diagnosis of AML. These novel and promising markers warrant validation in larger prospective studies.
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页数:10
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