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The prognostic relevance of miR-212 expression with survival in cytogenetically and molecularly heterogeneous AML
S M Sun1, V Rockova, L Bullinger
1Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Abstract:
Acute myeloid leukemia (AML) is a highly heterogeneous disease, characterized by various cytogenetic and molecular abnormalities, many of which may express prognostic value. MicroRNAs (miRNAs) are a class of small regulatory RNAs. The prognostic value of miRNAs in AML is yet to be determined. Here, we set out to identify miRNAs that are consistent significant prognostic determinants, independent from other known prognostic factors. A discovery cohort (n=167) and validation cohort (n=409) of a heterogeneous AML population were used to reliably identify miRNAs with prognostic value. We report miR-212 as an independent prognostic factor, significantly associated with a prolonged overall survival (OS) and also event-free and relapse-free survival in a discovery cohort (hazard ratio (HR)s=0.77, P=0.015 for OS) that was subsequently confirmed in an independent validation cohort of 409 cases (HR=0.83, P=0.016). The prognostic significance and the prevalence of high miR-212 did not correlate with specific (cyto)genetic subtypes of AML. High miR-212 expression levels are associated with a gene expression profile that is significantly enriched for genes involved in the immune response. MiR-212 may improve the current prognostic risk stratification of mixed AML including normal karyotype AML and AML with cytogenetic and molecular abnormalities.
Insights
MicroRNAs (miRNAs) can predict patient outcomes in Acute myeloid leukemia (AML). High miR-212 expression is linked to longer survival and may enhance AML risk stratification.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Acute myeloid leukemia (AML) is a complex blood cancer with diverse genetic features impacting prognosis.
- MicroRNAs (miRNAs) are small regulatory RNAs with emerging roles in cancer, but their prognostic value in AML requires further investigation.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) that serve as independent prognostic markers in Acute myeloid leukemia (AML).
- To validate the prognostic significance of identified miRNAs across independent patient cohorts.
Main Methods:
- Utilized a discovery cohort (n=167) and a validation cohort (n=409) of heterogeneous AML patients.
- Performed survival analyses to determine the association of miRNA expression with overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS).
- Correlated miRNA expression with cytogenetic subtypes and analyzed associated gene expression profiles.
Main Results:
- Identified miR-212 as a significant independent prognostic factor in AML.
- Demonstrated that high miR-212 expression is associated with prolonged OS, EFS, and RFS in both discovery (HR=0.77, P=0.015 for OS) and validation (HR=0.83, P=0.016) cohorts.
- Found no correlation between miR-212 prognostic significance and specific AML cytogenetic subtypes; high miR-212 expression correlated with immune response gene profiles.
Conclusions:
- miR-212 is a robust independent prognostic biomarker in Acute myeloid leukemia (AML).
- miR-212 expression levels can improve the prognostic risk stratification for various AML subtypes, including normal karyotype AML.
- The association of miR-212 with immune response pathways warrants further investigation into its biological mechanisms in AML.
