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Published on: October 26, 2017
Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia
Feng Zhi1, Xiangshan Cao, Xiaobao Xie
1Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
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.
Insights
Circulating microRNAs (miRNAs) show altered expression in acute myeloid leukemia (AML) patients. A panel of six miRNAs can distinguish AML from healthy donors, with miR-181b-5p potentially predicting patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Acute myeloid leukemia (AML) is a prevalent adult cancer with diverse genetic features.
- Circulating microRNAs (miRNAs) are emerging as potential noninvasive biomarkers for cancer diagnostics.
- Limited data exists on circulating miRNA profiles specific to AML patients.
Purpose of the Study:
- To investigate circulating miRNA expression patterns in adult acute myeloid leukemia (AML).
- To identify specific miRNAs that can differentiate AML patients from healthy individuals.
- To assess the prognostic value of identified miRNAs in AML.
Main Methods:
- Genome-wide serum miRNA expression analysis using Solexa sequencing.
- Validation of candidate miRNAs via real-time PCR assays.
- Analysis of training and verification sets from 140 AML patients and 135 healthy donors.
Main Results:
- Six miRNAs (miR-10a-5p, miR-93-5p, miR-129-5p, miR-155-5p, miR-181b-5p, miR-320d) showed significantly different expression in AML serum.
- A 6-miRNA signature effectively differentiated AML patients from normal controls (AUC 0.8129–0.9531).
- Serum miR-181b-5p levels correlated significantly with overall survival in AML patients.
Conclusions:
- Circulating miRNA expression patterns are systematically altered in AML.
- The identified 6-miRNA profile serves as a promising diagnostic biomarker for AML.
- miR-181b-5p demonstrates potential as a prognostic biomarker for AML survival.
