MicroRNAs as diagnostic biomarkers in cardiovascular diseases that cause sudden cardiac death: comparison between methods used in discovery and validation phases in major research studies

INTRODUCTION: MicroRNAs (miRNAs) are a non-coding RNA class of about 22 nucleotides that regulate gene expression by complementarily binding the 3’-untraslated regions of mRNA; thus, causing the inhibition of translation or mRNA degradation. A different expression profile of miRNAs (upregulated or downregulated) could lead to an imbalance in gene expression. EVIDENCE ACQUISITION: In recent years, many studies have focused on miRNAs and their role as biomarkers in diseases with difficult and inconclusive diagnoses. One of the most challenging diagnoses in the forensic field is sudden cardiac death (SCD) diagnosis which still has no comprehensive answers to the causes that determine the death of an apparently healthy subject. EVIDENCE SYNTHESIS: Thus, it could be interesting to study new biomarkers in genetic tests such as miRNAs. We have collected the most interesting studies in literature, focusing on the quantification methods used for the detection and validation of miRNAs with a potential role as biomarkers in arrhythmogenic cardiomyopathy, one of the most frequent pathological causes of SCD. CONCLUSIONS: In this review we will discuss the scientific logical path that starts from a discovery phase, using screening methods to select a group of differentially expressed miRNAs, up to a validation phase, which selects only informative miRNAs with a potential role as biomarkers.