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Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia.

ABSTRACT: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The disease is characterized by various cytogenetic and molecular abnormalities with distinct prognoses and gene expression profiles. Emerging evidence has suggested that circulating microRNAs (miRNAs) could serve as noninvasive biomarkers for cancer detection; however, little is known about circulating miRNA profiles in AML patients. In this study, a genome-wide serum miRNA expression analysis was performed using Solexa sequencing for initial screen, followed by validation with real-time PCR assays. The analysis was conducted on training and verification sets of serum samples from 140 newly diagnosed AML patients and 135 normal adult donors. After a two-phase selection and validation process, 6 miRNAs, miR-10a-5p, miR-93-5p, miR-129-5p, miR-155-5p, miR-181b-5p and miR-320d, were found to have significantly different expression levels in AML compared with control serum samples. Furthermore, unsupervised clustering analysis revealed the remarkable ability of the 6-miRNA profile to differentiate between AML patients and normal controls. The areas under the ROC curve for the selected miRNAs ranged from 0.8129 to 0.9531. More importantly, miR-181b-5p levels in serum were significantly associated with overall survival. These data demonstrated that the expression patterns of circulating miRNAs were systematically altered in AML and miR-181b-5p may serve as a predictor for overall survival in AML patients.

SUBMITTER: Zhi F

PROVIDER: S-EPMC3577716 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia.

Zhi Feng F Cao Xiangshan X Xie Xiaobao X Wang Biao B Dong Weimin W Gu Weiying W Ling Yun Y Wang Rong R Yang Yilin Y Liu Yan Y

PloS one 20130220 2

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The disease is characterized by various cytogenetic and molecular abnormalities with distinct prognoses and gene expression profiles. Emerging evidence has suggested that circulating microRNAs (miRNAs) could serve as noninvasive biomarkers for cancer detection; however, little is known about circulating miRNA profiles in AML patients. In this study, a genome-wide serum miRNA expression analysis was performed using Solexa s ...[more]

PMID: 23437222

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Project description:BACKGROUND:Treatment stratification based on bone marrow minimal residual disease (MRD) at set time points has resulted in considerably improved survival in pediatric acute lymphoblastic leukemia (ALL). Treatment response is assessed using bone marrow samples. MicroRNAs (miRs) easily traffic among fluid spaces and are more stable than most other RNA classes. We examined the role of circulating miRs as putative less invasive MRD biomarkers. METHODS:In an exploratory experiment, expression of 46 preselected miRs was studied in platelet-free blood plasma samples of 15 de novo, 5 relapsed ALL patients and 10 controls by Custom TaqMan Array Advanced MicroRNA Card. Based on their high expression in ALL compared to controls, and on the reduction observed along the induction therapy, four miRs were selected for further analyses: miR-128-3p, -181a-5p, -181b-5p and 222-3p. Their expression was measured by qPCR at 4 time points in 27 de novo ALL patients treated in the ALL IC-BFM 2009 study. RESULTS:The expression of all 4 miRs significantly decreased over the first week of therapy (miR-128-3p: log2 fold change - 2.86; adjusted p 3.6 × 10-7; miR-181b-5p: log2 fold change - 1.75; adjusted p 1.48 × 10-2; miR-181a-5p: log2 fold change -1.33; adjusted p 3.12 × 10-2; miR-222-3p: log2 fold change - 1.25; adjusted p 1.66 × 10-2). However, no significant further reduction in miR expression was found after the 8th day of therapy. Measured drop in expression of 2 miRs at day 8 strongly correlated with day 15 bone marrow flow cytometry MRD results (miR-128-3p: Pearson's r = 0.88, adjusted p = 2.71 × 10-4; miR-222-3p: r = 0.81, adjusted p = 2.99 × 10-3). CONCLUSION:In conclusion, these circulating miRs might act as biomarkers of residual leukemia. MiR-128-3p and miR-222-3p in blood predict day 15 flow cytometry MRD results 7 days earlier. Although, their sensitivity falls behind that of bone marrow flow cytometry MRD at day 15.

Dataset Information

Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia.

Publications

Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia.

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