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From Old to Bold: Advancing microRNA Studies in Sudden Cardiac Death Through Molecular Analysis of FFPE Heart Tissue
Alessia Bernini Di Michele1, Chiara Turchi1, Mauro Pesaresi1
1Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, Via Tronto, 60126 Ancona, Italy.
Insights
Archived formalin-fixed paraffin-embedded (FFPE) cardiac tissue can be used for microRNA (miRNA) analysis in molecular autopsy for sudden cardiac death (SCD). This approach supports identifying novel biomarkers when fresh tissues are unavailable.
Area of Science:
- Forensic pathology
- Molecular biology
- Cardiology
Background:
- Sudden cardiac death (SCD) is a significant global health issue with limited molecular investigation.
- Standard post-mortem genetic testing relies on blood or fresh tissue, which are often unavailable.
- DNA from formalin-fixed paraffin-embedded (FFPE) tissues is frequently unsuitable for conventional genetic analysis.
Purpose of the Study:
- To evaluate the utility of archived FFPE cardiac tissue for microRNA (miRNA) analysis in molecular autopsies.
- To explore the potential of FFPE tissues as a source for identifying molecular biomarkers in SCD.
Main Methods:
- A narrative review of studies investigating miRNA expression in FFPE cardiac tissue related to SCD.
- Critical analysis of ten selected studies meeting inclusion criteria.
Main Results:
- Differentially expressed miRNAs associated with SCD-relevant cardiac diseases have been identified in limited studies.
- MicroRNAs (miRNAs) are stable and detectable in FFPE tissues, even after fixation and storage.
- Studies demonstrate the feasibility and analytical reliability of miRNA profiling in archived FFPE cardiac specimens.
Conclusions:
- Archived FFPE cardiac tissues are valuable resources for molecular autopsy beyond historical or morphological data.
- FFPE tissues offer a promising matrix for SCD molecular investigations.
- This approach can aid in the identification and validation of novel molecular biomarkers for SCD.
Background/Objectives:
Sudden cardiac death (SCD) is a natural death of cardiac origin, accounting for an estimated 6-9 million deaths worldwide each year and representing a major public health challenge. Despite its clinical and forensic relevance, the molecular investigation of SCD remains limited. Peripheral blood or fresh tissue, the preferred specimens for post-mortem genetic testing, are not always available, and DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues is often suboptimal for conventional genetic analyses. This review evaluates the potential of archived FFPE cardiac tissue as a source for microRNA (miRNA) analysis in molecular autopsy.
Methods:
A narrative review was conducted by collecting studies investigating miRNA expression in FFPE cardiac tissue relevant to SCD. Ten studies met the inclusion criteria and were critically analyzed.
Results:
Although the available evidence remains limited, recent studies have identified several differentially expressed miRNAs associated with cardiac diseases relevant to SCD. Owing to their small size and remarkable stability, miRNAs remain detectable in FFPE tissues despite fixation and long-term storage, making them attractive molecular biomarkers. While most available studies were conducted in clinical rather than forensic settings, they demonstrate the feasibility and analytical robustness of miRNA profiling in archived FFPE cardiac specimens.
Conclusions:
This review underlines the importance of reconsidering archived FFPE tissues not merely as historical or morphological resources, but as promising matrices for molecular autopsy of SCD supporting the identification and validation of novel molecular biomarkers.
