Advancing Automated Methods for Microrna Profiling

The widespread influence of miRNAs in many biological processes and characteristic changes in expression profiles make them potential biomarkers for a range of diseases. With recent discoveries highlighting the enrichment of particular circulating miRNAs in plasma under pathological conditions, there has been a push for technological advances in miRNA profiling studies as a diagnostic tool. A standardized, automated, high-throughput method for miRNA isolation from human plasma samples was developed in this study. Samples were subject to full miRNome profiling utilizing RT-qPCR. These unique findings demonstrate that developing a distinct miRNA biomarker profile for heart failure patients is feasible and holds potential diagnostic value

Identification of a Novel microRNA Profile in Pediatric Cancer Patients treated with Anthracycline Chemotherapy.

INTRODUCTION: Anthracycline chemotherapy (AC) is associated with decline in left ventricular ejection fraction (LVEF), yet mechanisms remain unclear. While changes in microRNAs (miRs) have been identified in adult cardiovascular disease, miR profiles in pediatric AC patients have not been well studied. The goal of this study was to examine miR profiles (unbiased array) in pediatric AC patients compared to age matched referent normal patients. HYPOTHESIS: Pediatric AC patients will express a unique miR profile at initiation and completion of therapy related to LVEF. METHODS: Serum was collected in pediatric patients (n=12, 10-22yrs) with newly diagnosed malignancy requiring AC within 24-48 hours following initiation of therapy (30-60 mg/m RESULTS: LVEF fell from AC initiation at ~1yr following AC (64.28% ± 1.78% vs 57.53% ± 0.95% respectively, p=0.004). Of the 84 miRs profiled, significant shifts in 17 miRs occurred relative to referent normal (p ≤ 0.05). Moreover, the functional domain of miRs associated with myocardial differentiation and development fell over 3-fold at completion of AC (p ≤ 0.05). Lastly, 3 miRs were associated with the fall in LVEF (p ≤ 0.05). CONCLUSIONS: This study demonstrated for the first time that changes in miR expression occurs in pediatric AC patients. These findings suggest that miRs are a potential strategy for early identification of AC patients susceptible to LV dysfunction

Use of integrated imaging and serum biomarker profiles to identify subclinical dysfunction in pediatric cancer patients treated with anthracyclines

Abstract Background Anthracycline induced cardiomyopathy is a major cause of mortality and morbidity among pediatric cancer survivors. It has been postulated that oxidative stress induction and inflammation may play a role in the pathogenesis of this process. Accordingly, the present study performed an assessment of biomarker profiles and functional imaging parameters focused upon potential early determinants of anthracycline induced cardiomyopathy. Methods Patients (10–22 years) were prospectively enrolled between January 2013 and November 2014. Thirteen subjects completed the study and underwent serial cardiac magnetic resonance imaging and plasma biomarker profiling performed 24–48 h after the first anthracycline dose and at set dose intervals. In addition, we collected plasma samples from 62 healthy controls to examine normal plasma biomarker profiles. Results Left ventricular ejection fraction (LVEF) decreased from 64.3 ± 6.2 at the first visit to 57.5 ± 3.3 (p = 0.004) 1 year after chemotherapy. A decline in longitudinal strain magnitude occurred at lower cumulative doses. A differential inflammatory/matrix signature emerged in anthracycline induced cardiomyopathy patients compared to normal including increased interleukin-8 and MMP levels. With longer periods of anthracycline dosing, MMP-7, a marker of macrophage proteolytic activation, increased by 165 ± 54% whereas interleukin-10 an anti-inflammatory marker decreased by 75 ± 13% (both p < 0.05). MMP7 correlated with time dependent changes in EF. Conclusions Asymptomatic pediatric patients exposed to anthracycline therapy develop abnormal strain parameters at lower cumulative doses when compared to changes in EF. A differential biomarker signature containing both inflammatory and matrix domains occur early in anthracycline treatment. Dynamic changes in these domains occur with increased anthracycline doses and progression to anthracycline induced cardiomyopathy. These findings provide potential prognostic and mechanistic insights into the natural history of anthracycline induced cardiomyopathy. Trial registration number NCT03211520 Date of Registration February 13, 2017, retrospectively registered