Abstract
Background: Trisomy 8 is the most frequent chromosomal abnormality in Korean patients with myelodysplastic syndrome (MDS). MicroRNA (miRNA) deregulation contributes to hematological malignancies, including MDS, and cancer-associated genomic regions are known to encode miRNAs. The aim of the present study was to investigate whether expression of miRNAs encoded by chromosome 8, which is the most frequent abnormal chromosome in MDS in Korean patients, is upregulated. Further, we analyzed the association of the upregulated miRNAs with clinical outcome.
Methods: Sixty-five MDS patients and 11 controls were enrolled in the study. miRNAs were extracted from archived unstained bone marrow aspirate slides of the subjects. The TaqMan microRNA assay was used to detect 13 miRNAs encoded by chromosome 8 (miR-30b-5p, miR-30d-5p, miR-124-3p, miR-151a-5p, miR-320a, miR-383-5p, miR-486-5p, miR-596, miR-597-5p, miR-598-5p, miR-599, miR-661, and miR-875-5p) and an endogenous control RNU48. The Ct value of each miRNA and RNU48 was obtained and the 2-deltaCt (deltaCt = CtmiRNA – CtRNU48) for each miRNA was calculated. Clinical data and laboratory data (complete blood cell counts, bone marrow blasts, and karyotyping data) were obtained from patients' medical records. The Mann–Whitney test was used to compare the miRNA expression profile of the patients with that of the controls. Overall survival was analyzed by the Kaplan-Meier Method and Cox's proportional hazard model.
Results: The expression of miR-320a and miR-661 was significantly higher in MDS patients than in the controls. Other miRNAs were not significantly upregulated. The expression of miR-320a was 22.30±110.15 (mean±SD) in patients and 4.96±9.56 in controls (P = 0.016). The expression of miR-661 was 0.39±1.72 in patients and 0.05±0.08 in controls (P = 0.021). The patients were divided into 2 groups—patients with high miR-661 expression and patients with low miR-661 expression—using an arbitrary cut-off of miR-661 expression of 0.1. The patients with high miR-661 expression showed significantly decreased overall survival (P = 0.048) (Fig. 1). Blast counts and poor cytogenetics were also significantly associated with the significantly decreased overall survival (all P < 0.001) Hemoglobin and platelet counts showed borderline significance in overall survival (P = 0.068 and P = 0.066, respectively). Multivariate analyses using Cox's proportional hazard model revealed that high miR-661 expression was an independent prognostic variable (P = 0.024) with a hazard ratio of 3.613 (CI; 1.189-11.0). Poor cytogenetics was also found to be an independent prognostic variable (P = 0.047).
Conclusion: This is the first report of the association between upregulation of miR-661 and MDS. Although these findings need to be validated by studies on a large number of patients, high expression of miR-661 may have the potential for use as an adverse prognostic marker for Korean patients with MDS.
Fig 1. Overall survival analysis of patients with according to miR-661 expression Fig 1. Overall survival analysis of patients with according to miR-661 expression
Disclosures
No relevant conflicts of interest to declare.
Generalized log-logistic proportional hazard model with applications in survival analysis
