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MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier (MSC) for Lung Cancer Screening
Published on: October 26, 2017
MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with
M Díaz-Beyá1, S Brunet2, J Nomdedéu3
11] Hematology Department, Hospital Clinic, Institut d'Investigacions Bomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain [2] Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain.
Abstract:
Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.
Insights
Four microRNAs (miRNAs) show prognostic value in intermediate-risk acute myeloid leukemia (AML). Specific miRNA levels correlate with overall survival and relapse risk, aiding personalized treatment strategies for AML patients.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Acute myeloid leukemia (AML) is a complex blood cancer with variable treatment outcomes.
- Prognostic factors, including cytogenetics and molecular markers, are crucial for tailoring AML therapy.
- MicroRNAs (miRNAs) are increasingly recognized for their role in AML pathogenesis and prognosis.
Purpose of the Study:
- To investigate the association between miRNA expression and clinical outcomes in intermediate-risk cytogenetic AML (IR-AML).
- To identify specific miRNAs that can serve as prognostic markers for IR-AML patients.
Main Methods:
- miRNA expression profiling of 670 miRNAs in 85 IR-AML patients.
- Validation of 10 candidate miRNAs in a larger cohort of 238 IR-AML patients using individual assays.
- Statistical analysis to determine the independent prognostic impact of miRNAs on overall survival and relapse risk.
Main Results:
- Ten outcome-related miRNAs were initially identified.
- Four miRNAs (miR-196b, miR-644, miR-135a, and miR-409-3p) were confirmed as prognostic markers in the total cohort.
- High miR-196b and miR-644 levels correlated with shorter overall survival.
- Low miR-135a and miR-409-3p levels were associated with a higher risk of relapse.
- Specific miRNAs retained prognostic value within distinct molecular subgroups (e.g., NPM1, CEBPA, FLT3-ITD status).
Conclusions:
- miR-409-3p, miR-135a, miR-196b, and miR-644 are significant independent prognostic markers for IR-AML.
- These miRNAs offer valuable prognostic information both overall and within specific molecular subgroups of IR-AML.
- The findings support the use of these miRNAs in refining risk stratification and guiding treatment decisions for IR-AML patients.
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