Circulating Cell-Free Nucleic Acids as Epigenetic Biomarkers in Precision Medicine

Abstract

The circulating cell-free nucleic acids (ccfNAs) are a mixture of single-or doublestranded nucleic acids, released into the blood plasma/serum by different tissues via apoptosis, necrosis, and secretions. Under healthy conditions, ccfNAs originate from the hematopoietic system, whereas under various clinical scenarios, the concomitant tissues release ccfNAs into the bloodstream. These ccfNAs include DNA, RNA, microRNA (miRNA), long non-coding RNA (lncRNA), fetal DNA/RNA, and mitochondrial DNA/RNA, and act as potential biomarkers in various clinical conditions. These are associated with different epigenetic modifications, which show disease-related variations and so finding their role as epigenetic biomarkers in clinical settings. This field has recently emerged as the latest advance in precision medicine because of its clinical relevance in diagnostic, prognostic, and predictive values. DNA methylation detected in ccfDNA has been widely used in personalized clinical diagnosis; furthermore, there is also the emerging role of ccfRNAs like miRNA and lncRNA as epigenetic biomarkers. This review focuses on the novel approaches for exploring ccfNAs as epigenetic biomarkers in personalized clinical diagnosis and prognosis, their potential as therapeutic targets and disease progression monitors, and reveals the tremendous potential that epigenetic biomarkers present to improve precision medicine. We explore the latest techniques for both quantitative and qualitative detection of epigenetic modifications in ccfNAs. The data on epigenetic modifications on ccfNAs are complex and often milieu-specific posing challenges for its understanding. Artificial intelligence and deep networks are the novel approaches for decoding complex data and providing insight into the decision-making in precision medicine.

Circulating Free DNA and Its Emerging Role in Autoimmune Diseases

“…Overall, DNA methylation also seems to be a promising alternative for early diagnosis and monitoring of the autoimmune diseases [ 111 ]. The analysis of changes in cfDNA methylation levels suggest potential to stratify patients depending on different stages in the diseases, but could also serve to monitor the response to specific treatments [ 5 ]. By using tissue/disease-specific epigenetic marks on the cfDNA, it might be possible to offer personalized medicine to manage the autoimmune diseases in the future.…”

“…Although little is known about the precise function of cfDNA in autoimmunity, the advent of more sensitive methods and the increasing understanding of the role of DNA sensing receptors in inflammation and autoimmunity have clearly expanded interest in cfDNA analyses. CfDNA can also associate with different epigenetic modifications, being potential biomarkers in autoimmune diseases [ 5 ]. Therefore, in the present review, we provide an overview of the basic biology of cfDNA and the evolution of cfDNA in autoimmune diseases as a biomarker of disease activity, progression, and prediction of the treatment response.…”

Impacts of Epigenetic Processes on the Health and Productivity of Livestock

“…In addition, the dynamic changes due to extra- or intraenvironmental cellular conditions and disease progression or evolution in response to environmental factors are one advantage of epigenetic biomarkers when compared with stable (not changing) genetic biomarkers based on gene sequence ( García-Giménez et al, 2016 ). Association of genetic biomarkers to phenotypes is often inconsistent across studies, while epigenetic markers are promising substitutes for the timely diagnosis and monitoring of diseases ( Rahat et al, 2020 ). Furthermore, epigenetic markers being tissue specific reflect the pattern of disease progression ( Zeng et al, 2019 ).…”

Isolation of Cell-Free miRNA from Biological Fluids: Influencing Factors and Methods

“…To date, there is no universally accepted hypothesis on generation of free cf-miRNA pool. Some types of miRNA–bearing complexes could be actively secreted (exosomes) [ 106 ], while for others passive leakage from damaged or dying cells is more feasible [ 107 , 108 ]. Another unknown is how, presumably, different clearance rates of different complexes could impact the half-life of different populations of cf-miRNA.…”