Increased Expression of Circulating Mir-22 in the Peripheral Blood of Patients with Myelodysplastic Syndromes Was Associated with Poorer Prognosis

The molecular pathogenesis of myelodysplastic syndromes (MDS) has not been completely elucidated. Deregulation of expression of some microRNA has been implicated in hematological disorders including MDS. An oncogenic role for miR-22 was recently suggested in MDS in which the expression of miR-22 was increased. However, there were corroborations showing that it could be a tumor suppressor in acute myeloid leukemia. In this study, we examined the expression levels of circulating miR-22 in the plasma of patients with MDS and evaluated its significance in clinical context. The diagnosis of MDS was made according to the WHO classifications and subtypes included 8 cases of RA, 14 cases of RCMD and 6 cases of RARS/RCMD-RS, 10 cases RAEB1 and 7 cases RAEB2. Twenty cases of healthy donors were enrolled as normal control. Written informed consent for sample collection was obtained from all subjects enrolled. EDTA-anticoagulated peripheral blood samples were collected and centrifuged. Circulating microRNAs were purified from the plasma with miRNeasy serum kit (Qiagen). Expression of miR-22 was reverse- transcripted and measured with stem-loop real time quantitative polymerase chain reaction assay. First of all, we proved that the expression of miR-22 was detectable in the plasma of patients with MDS as well as of healthy donors. Our result showed that the expression levels of circulating miR-22 in MDS patients were higher than that in healthy donors (medians 1.360 vs 1.000, P<0.05), among which 13 patients (37.1%) showed marked increase of miR-22 expression (>2 times). Due to the high heterogeneity of MDS and relatively smaller sample size, the subtypes were grouped into two major categories based on IPSS: the low-risk group (including RA, RCMD and RARS/RCMD-RS, totally 18 cases) and the high-risk group (RAEB1 and RAEB2, 17 cases in total). Relative levels of circulating miR-22 were higher in the high-risk group than in the low-risk group (medians= 1.081 vs 2.317, P<0.05). A follow-up study revealed an association of the expression levels of miR-22 with prognosis. Patients with increased expression of miR-22 had poorer clinical response (Chi-square analysis, P<0.05) and lower overall survival rate (Kaplan-Meier analysis, P<0.05). We compared the levels of miR-22 in the plasma with that of mononuclear cells of bone marrow in some MDS patients and found that the relative levels of miR-22 in the plasma and bone marrow cells were not directly co-related (P>0.05), indicating it could be an independent prognostic factor. In summary, this study confirmed an oncogenic presence of miR-22 in MDS. Given the fact that there is a lack of blastic cells in the bone marrow of patients with low-risk MDS but their plasma or serum is easy to obtain, the detection of circulating miR-22 may be of value as a molecular marker in the prognosis of MDS.