Epigenetic biomarkers: Current strategies and future challenges for their use in the clinical laboratory

Abstract

Epigenetic modifications and regulators represent potential molecular elements which control relevant physiological and pathological features, thereby contributing to the natural history of human disease. These epigenetic modulators can be employed as disease biomarkers, since they show several advantages and provide information about gene function, thus explaining differences among patient endophenotypes. In addition, epigenetic biomarkers can incorporate information regarding the effects of the environment and lifestyle on health and disease, and monitor the effect of applied therapies. Technologies used to analyze these epigenetic biomarkers are constantly improving, becoming much easier to use. Laboratory professionals can easily acquire experience and techniques are becoming more affordable. A high number of epigenetic biomarker candidates are being continuously proposed, making now the moment to adopt epigenetics in the clinical laboratory and convert epigenetic marks into reliable biomarkers. In this review, we describe some current promising epigenetic biomarkers and technologies being applied in clinical practice. Furthermore, we will discuss some laboratory strategies and kits to accelerate the adoption of epigenetic biomarkers into clinical routine. The likelihood is that over time, better markers will be identified and will likely be incorporated into future multi-target assays that might help to optimize its application in a clinical laboratory. This will improve cost-effectiveness, and consequently encourage the development of theragnosis and the application of precision medicine.

Prospects for incorporation of epigenetic biomarkers in human health and environmental risk assessment of chemicals

“…Even temporary epigenetic changes can influence and compromise cell states (Ladd‐Acosta, ; Schmidl et al ., ). Therefore, epigenetic marks are interesting candidates to link environmental exposure to cell and organismal phenotype alterations through the development of epigenetic biomarkers (Mulero‐Navarro & Esteller, ; Mirbahai & Chipman, ; Ladd‐Acosta, ; García‐Giménez et al ., ). Such epigenetic signatures may be useful in the prediction of life health outcomes from a specific early life exposure or, in some cases, even from in utero exposure (Ray, Yosim & Fry, ; Marsit, ; Laufer et al ., ; Alvarado‐Cruz et al ., ).…”

“…Epigenetic signatures fulfil several important criteria for a biomarker. They bear long‐term stability and are relatively easy to detect, they are highly selective, and they are sensitive to environmental stressors, providing information about changes in exposure at different times and different concentrations/doses (Chan & Baylin, ; Nogueira da Costa & Herceg, ; García‐Giménez et al ., ; Prince et al ., ). Therefore, epigenetic biomarkers present several advantages compared to other regularly used transcriptional biomarkers (see Section II and Table for an appraisal of these biomarkers): epigenetic biomarkers can be more accurate, specific, stable and easily measured (Chan & Baylin, ; Ladd‐Acosta, ; García‐Giménez et al ., ; Leygo et al ., ).…”

“…They bear long‐term stability and are relatively easy to detect, they are highly selective, and they are sensitive to environmental stressors, providing information about changes in exposure at different times and different concentrations/doses (Chan & Baylin, ; Nogueira da Costa & Herceg, ; García‐Giménez et al ., ; Prince et al ., ). Therefore, epigenetic biomarkers present several advantages compared to other regularly used transcriptional biomarkers (see Section II and Table for an appraisal of these biomarkers): epigenetic biomarkers can be more accurate, specific, stable and easily measured (Chan & Baylin, ; Ladd‐Acosta, ; García‐Giménez et al ., ; Leygo et al ., ). Other relative advantages are that: ( i ) epigenetic marks are accessible in body fluids, avoiding the need for biopsy specimens as sometimes required for the development and monitoring of transcriptional biomarkers; ( ii ) epigenetic mechanisms are usually involved in the initial stages of disease development, and therefore epigenetic biomarkers have the potential to be better suited than transcriptional biomarkers for early diagnosis; ( iii ) different stages and types of cancer have unique methylation signatures, and such signatures could be targets in the development of specific and accurate biomarkers to assist in tumour‐type evaluation as well as prognosis and disease management (Costa‐Pinheiro et al ., ; García‐Giménez et al ., ; Leygo et al ., ).…”

Epigenetics in disease etiopathogenesis

“…Epigenetic modifications detection could successfully be translated as biomarkers into clinical medicine, since it provides insight into functioning of genes and explains phenotypic differences between healthy and diseased individuals. The epigenetic modifications could also be used as biomarkers for determination of environmental factors affecting health and disease onset, and also as diagnostic and prognostic biomarkers in oncology, endocrinology, cardiology, and neuropsychiatry (GARCÍA-GIMÉNEZ, et al 2017;METZINGER, et al 2017;SANDOVAL, et al 2013).…”

The anti-lipidemic drug simvastatin modulates Epigenetic Biomarkers in the AmphipodGammarus locusta

“…Therefore, the integration of these proteins as potential biomarkers of epigenetic regulation is critical for an improvement of hazard and risk assessment. These biomarkers can potentially predict adverse outcome effects along the organism's lifecycle [57,58], representing inherent, stable and robust mechanisms of memory of environmental exposures [59] and thus potentially providing an easy, sensitive and accurate tool to address changes after environmental exposures [60].…”