Abstract 1954: Circulating microRNA-21 predicts the response to hypomethylating agents in patients with myelodysplastic syndromes.

Abstract

Abstract Background: Although hypomethylating agents therapy have considerably improved the outcomes of patients with myelodysplastic syndromes (MDS), the discovery of sensitive non-invasive biomarkers that can facilitate the prediction of response to hypomethylating agents (HMA) and therapeutic outcomes are highly desirable to determine optimized strategies of epigenetic therapy for MDS. Circulating microRNAs have been evaluated as potential biomarkers for cancer diagnosis and prognosis prediction. Purpose: We evaluated the significance of miR-21 expression in serum as a biomarker for predicting response in MDS patients treated with HMA. Patients and methods: Serum miR-21 level was measured by quantitative real-time PCR in 58 MDS patients at diagnosis and 14 healthy controls. We analyzed the correlation between serum miR-21 level and clinical characteristics and response to HMA and survival. Results: We found that serum miR-21 level was significantly downregulated in patients with MDS than those in healthy controls (P<0.001). Moreover, miR-21 level was significantly lower in patients with response (CR, mCR, PR and SD with HI) to HMA compared to those without response (median, 0.9414±0.6349 vs. 1.1443±0.7707; P=0.041). Receiver-operator characteristic curve analysis indicated that serum miR-21 was useful in differentiating responder from non-responder with AUC of 0.648. At a cut-off value of 1.2613 for serum miR-21 level, the optimal sensitivity and specificity were 83.3% (95% CI: 68.6-93.3%) and 45.8% (95%CI: 25.5-67.1%), respectively. Patients, whose miR-21 level at diagnosis was higher than cutoff level, were defined as high miR-21 group (n=17) and the low miR-21 group representing the remaining 41 patients. We found that patients in high miR-21 grooup, compared with those in low miR-21 group, had a shorter median PFS (P=0.001). On multivariate analysis, Serum miR-21 level remained as a significant prognostic factor for response to HMA and PFS. Conclusion: In this study, we evaluated the levels of serum miR-21 in patients with MDS, and found that serum miR-21 level predicts response to HMA and PFS in MDS. Although this prognostic significance should be validated in an independent set of patients receiving HMA, serum miR-21 level is a promising biochemical marker for response prediction to HMT. Citation Format: Yoo Hong Min, Jae Yong Cho, Yundeok Kim, Yeo-Kyeoung Kim, Soo Jeong Kim, Jin Seok Kim, June-Won Cheong, Hyeuong Joon Kim. Circulating microRNA-21 predicts the response to hypomethylating agents in patients with myelodysplastic syndromes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1954. doi:10.1158/1538-7445.AM2013-1954