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. 2018 Jun 8;9(44):27333-27345.
doi: 10.18632/oncotarget.25542.

A pilot study of circulating microRNAs as potential biomarkers of Fabry disease

Giuseppe Cammarata  1 , Simone Scalia  1 , Paolo Colomba  1 , Carmela Zizzo  1 , Antonio Pisani  2 , Eleonora Riccio  2 , Michaela Montalbano  1 , Riccardo Alessandro  1   3 , Antonello Giordano  4 , Giovanni Duro  1
Affiliations

A pilot study of circulating microRNAs as potential biomarkers of Fabry disease

Giuseppe Cammarata et al. Oncotarget. .

Abstract

Patients suffering from Fabry disease (FD), a lysosomal storage disorder, show a broad range of symptoms and the diagnosis followed by the therapeutic decision remains a great challenge. The biomarkers available today have not proven to be useful for predicting the evolution of the disease and for assessing response to therapy in many patients. Here, we used high-throughput microRNA profiling methodology to identify a specific circulating microRNA profile in FD patients. We discovered a pattern of 10 microRNAs able to identify FD patients when compared to healthy controls. Notably, two of these: the miR199a-5p and the miR-126-3p are able to discriminate FDs from the control subjects with left ventricular hypertrophy, a frequent but non-specific FD symptom. These same microRNAs are also sensitive to enzyme replacement therapy showing variation in the subjects under treatment. Furthermore, two other microRNAs of the profile, the miR-423-5p and the miR-451a, seem useful to highlight cardiac involvement in FD patients. A literature and database search revealed that miR-199a-5p, miR-126-3p, miR-423-5p and miR-451a are known to be linked to pathological states that occur during the FD development. In particular, miR-199a-5p, and miR-126-3p are involved in endothelial dysfunction and miR-423-5p and miR-451a in myocardial remodeling. In conclusion, in this study we identified a common plasma microRNA profile in FD patients, useful not only for the correct classification of Fabry patients regardless of sex and age, but also to evaluate the response to therapy. Furthermore, our observations suggest that some microRNAs of this profile demonstrate prognostic qualities.

Keywords: ERT; Fabry disease; LVH; Pathology; biomarker; microRNA.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1. Hierarchical clustering of 18 differentially expressed microRNAs (P ≤ 0.05 & FC 1.5) obtained from the Fabry patients (FD) versus normal controls (NC) comparison
Data from Nanostring profiling of Cohort1 participants.
Figure 2
Figure 2. Scatter plots and ROC plots for the 10 validated miRNAs differentiating Fabry patients (FD) and normal controls (NC) (cohort 2)
All values were normalized with respect to the lowest samples and plotted on the Y-axis. Data from RT-qPCR assays. (AUC: area under the curve).
Figure 3
Figure 3. Scatter plots of the 4 miRNAs differentiating Fabry patients (FD) and symptomatic controls with left ventricular hypertrophy (LVH) (P value ≤ 0.05)
All values were normalized with respect to the lowest samples and plotted on the Y-axis. Data from RT-qPCR assays.
Figure 4
Figure 4. Scatter plots and ROC plots of miR-423-5p and miR-451a levels in symptomatic controls with left ventricular hypertrophy (LVH) with respect to normal controls (NC)
All values were normalized with respect to the lowest samples and plotted on the Y-axis. Data from RT-qPCR assays. (AUC: area under the curve).
Figure 5
Figure 5. Comparison of the miR-126-3p, miR-199a-5p, miR-423-5p, miR-451a levels from ERT-treated Fabry patients (ERT) with respect to naïve Fabry patients (FD), normal controls (NC) and symptomatic controls with left ventricular hypertrophy (LVH)
All values were normalized with respect to the lowest samples and plotted on the Y-axis. Data from RT-qPCR assays.
See this image and copyright information in PMC

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