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ARC. miR-223-3p and miR-19b-3p were positively associ- ated with an LDH level. miR-3200-3p was also positively associated with ANC (r=0.911, P=0.012), and miR-196a- 5p, miR-15a-3p, miR-133b, miR-106b-5p, and miR-4267 with ALC (Online Supplementary Table S4).
miR-126-5p as a candidate biomarker of response to IST in SAA
We next sought to investigate effects of IST on exoso- mal miRNA profiles after six months of treatment in 40 SAA patients. PCA was performed to detect miRNAs in SAA patients before and after IST (Online Supplementary Figure S3). miR-143-3p (P=0.033), miR-324-3p (P=0.001),
A
miR-1180-3p (P=0.009), miR-126-5p (P=0.008), and miR- 382-5p (P=0.009) were significantly decreased after treat- ment (Online Supplementary Figure S4). Subsequently, SAA patients were classified into either SAA-responders (com- plete or partial response) or SAA-non-responders after six months of therapy based on standard clinical parameters, and miRNA expression profiles were then compared before and after IST. No variations were observed after IST for any miRNAs in SAA-non-responders. In SAA- responders, miR-4651 (P=0.015) and miR-126-5p (P=0.025) were significantly reduced after treatment (Figure 4A). However, only miR-126-5p (AUC, 0.79) dis- played a strong association with the response to IST in
B
Figure 3. Exosomal miRNAs in severe aplastic anemia (SAA) and myelodysplastic syndromes (MDS) patients. Relative expression levels of the 48 miRNAs were calculated as Log2FC and shown for each group [SAA, MDS, and healthy controls (HC)]. (A) 7 exosomal miRNAs differentially expressed in both SAA and MDS com- pared to HC. (B) Receiver operating characteristic (ROC) curves for 4 miRNAs in AA and MDS. The ROC curve of the miRNA panel was generated based on the pre- dicted probability for each patient and using the healthy group as a control. P<0.05 was considered statistically significant. AUC: area under the curve; CI: Confidence Interval.
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