Circulatory Epigenetic Signatures: A Promise for Early Detection of Cancer, Cardiovascular and Neurodevelopmental Diseases

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Background

Alterations in one-carbon metabolism cycle may be in charge of abnormal DNA methylation processes, which could result in a number of human disorders. Accumulating evidence indicates that many human diseases with multi-factorial origin may also have an epigenetic basis and it has been possible to map the epigenetic signatures of diagnostic/prognostic relevance with the advancement of methods to study them.

Epigenetic alterations including aberrant DNA methylation, histone modification, and dysregulated expression of miRNAs play a significant part in cancer initiation and progression. CpG island hypermethylation is a putative method for the inactivation of tumour suppressor genes by transcriptional silencing. Tumour specific aberrant promoter hypermethylation of genes is a frequent early event in cancer which may be detected in body fluids and has been found in patients with several tumour types, including lung, prostate, breast, and colorectal cancer. In both early-stage and advanced-stage cancers circulating cell free DNA levels (CFDNA) in serum are unusually high, therefore liquid biopsy-based approaches provide an accurate and noninvasive method for early-stage detection of solid and liquid cancer. Cells in cancer tissue may opt for any two mechanisms, either they undergo in situ apoptosis and/or necrosis or they may separate from tumours and extravagate into the circulation and lysed. Thus, aberrant DNA methylation patterns in body fluids/liquid biopsies can be indicative of disease presence and may be used as a biomarker for the diagnosis and treatment of cancer patients.

The onset and progression of neurodegenerative/neurodevelopmental and other age-related diseases may be significantly influenced by environmental factors, according to DNA methylation studies based on transgenic Alzheimer's disease mouse models, which revealed genome-wide hypomethylation in these patients. These mice models showed severe learning and memory deficits as well as reduced synaptic plasticity due to downregulation of DNMT3a mRNA levels in various somatic, germinal, and serum samples. Reduced global hypomethylation could therefore be a useful new diagnostic biomarker for many common disorders. In case of traumatic brain injury (TBI), the blood–brain barrier gets impaired and leaky resulting cell free nucleic acids as potential biomarkers. Neurodegenerative disorders have also been linked to variations in both global and locus-specific levels of5mC and 5hmC.

Epigenetic regulation is crucial in the pathogenesis of cardiovascular diseases like hypertension and atherosclerosis, and recent advances on the alteration, regulation, and implication of histone modifications and DNA methylation in cardiac injury and heart dysfunction will pave a way towards novel diagnostic approaches leading to improvement of survival rates. Circulating miRNAs have been recognized as critical biomarkers for myocardial infarction, coronary heart disease, and heart failure. Also, they have been identified to govern pulmonary vascular alterations related to the onset of pulmonary arterial hypertension and/or influence cellular responses to hypoxia. On the other hand, circulating long ncRNAs serve as specific and sensitive biomarkers for not only cardiovascular disease but also therapeutic response. Together, these data provide credence to the idea that epigenetic changes can affect risk for complex diseases.

Cellular identity and function depend on the precise expression of genes. Different epigenetic mechanisms control the chromatin structure and DNA accessibility to the transcriptional machinery, including DNA methylation, histone modifications, non-coding RNA expressions, and miRNA expressions. Numerous disease pathogenesis disorders have been linked to altered epigenetic signatures and mechanisms. Personalized epigenetic maps for diagnosis and treatment are strengthened by new epigenetic signatures, mechanisms and targets involved in diseases such as cancer, neurodevelopmental disorders and cardiovascular diseases, according to studies. As a result, we suggest that Original research papers and reviews focusing on the use of circulating epigenetic signatures as therapeutic targets and biomarkers for diagnosis will be considered for this Research Topic. Further, manuscripts exploring the epigenetic signatures/markers and mechanisms involved in solid and liquid cancers, neurodevelopmental disorders and cardiovascular disease diagnosis and treatment are encouraged.

The goal of this article collection is to compile the results of research in the fields connected to the role and applications of circulatory epigenetic signatures in early detection of Cancer, Cardiovascular and Neurodevelopmental Disorders. Submission of papers having clear ties to related topics is greatly encouraged. Before being accepted, the contributions to this collection will go through peer review.

Keywords: epigenetics, cancer, cardiovascular disease, neurodevelopmental disorder, therapeutic target, circulatory epigenetic signature

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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