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Epigenomes
Special Issues
The Use of Epigenetic Biomarkers as Diagnostic and Therapeutic Options
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The Use of Epigenetic Biomarkers as Diagnostic and Therapeutic Options

A special issue of Epigenomes (ISSN 2075-4655).

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 12750

Special Issue Editors

Dr. Yuen Yee Cheng

E-Mail Website
Guest Editor
Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW 2007, Australia
Interests: cancer epigenetic; molecular diagnostics; DNA methylation; microRNA; non-invasive diagnostic; tumour suppressor
Special Issues, Collections and Topics in MDPI journals
Dr. Kenneth Lee

E-Mail Website
Guest Editor
NSW Health pathology, Sydney Medical School, University of Sydney, Australia
Interests: haematolymphoid pathology; pulmonary pathology; dendritic cell and lymphoid CD markers; histone modifications

Special Issue Information

Dear Colleagues,

Epigenetic changes are the key processes driving cellular aging, development and carcinogenesis. Epigenetic dysregulation is a universal feature of neoplasms and is considered a hallmark of cancer; subsequently, the study of the epigenome has attracted considerable attention for developing biomarker detection methods and therapeutic discovery for various malignancies for over a decade. The study of epigenetic changes has prompted the discovery of new treatments in cancer with many obtaining FDA approval to be used in clinical practices. However, comprehensive studies are still required for the movement of epigenetic-based therapeutic options for various types of diseases with distinct epigenetic signatures.

Amongst all epigenetic alterations, DNA methylation is the most widely studied in cancer. The status of DNA methylation changes during different stages of carcinogenesis and is readily identifiable using current technology. As such, the status of DNA methylation has biomarker potential in cancer diagnostics. Epigenetic changes can be measured in cell free DNA (CFDNA) which is abundant in blood samples such as plasma and serum. Although this is an area of great diagnostic potential, it is yet to be employed in a clinical setting demonstrating the important requirement for further characterisation in this area.

The advantage of using epigenetic changes as biomarkers is their stability and availability in many sample types. With modern technology the detection of epigenetic changes can also be useful as detection tools in non-invasive biospecimens such as blood plasma and serum. Epigenetic changes are also useful for treatment discovery, as different malignancies present with different epigenetic signatures and therefore reversal of this phenotype presents as a targetable therapy. For example, global DNA hypermethylation can be reversed with demethylation agents such as decitabine while histone modification alterations can be attenuated with TSA or SAHA. Additionally, downregulated tumour suppressor microRNA expression can be restored by synthetic microRNA replacement therapy.

The present Special Issue aims to publish high-quality research articles as well as review contributions on a variety of topics related to epigenetic biomarkers detection in non-invasive clinical samples.

Potential topics include, but are not limited to:

  • Types of Epigenetic biomarkers used in clinical practices for different diseases
    • DNA methylation, circulating or non-circulating
    • Histone modification e.g., histone methylation and acetylation
    • microRNA and other non-coding RNA
  • Methods of new epigenetic biomarkers discovery;
  • The potential of liquid biopsy for epigenetic biomarkers detection;
  • The process of developing of epigenetic biomarker as treatment options for clinical practices;

Dr. Yuen Yee Cheng
Dr. Kenneth Lee
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Epigenomes is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

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Research

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10 pages, 974 KiB  
Article
Application of the High-Throughput TAB-Array for the Discovery of Novel 5-Hydroxymethylcytosine Biomarkers in Pancreatic Ductal Adenocarcinoma
by Chang Zeng, Zhou Zhang, Jun Wang, Brian C-H Chiu, Lifang Hou and Wei Zhang
Epigenomes 2019, 3(3), 16; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3030016 - 10 Aug 2019
Cited by 11 | Viewed by 3760
Abstract
The clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) remain dismal, with an estimated five-year survival rate of less than 5%. Early detection and prognostic approaches, including robust biomarkers for PDAC, are critical for improving patient survival. Our goal was to explore the biomarker [...] Read more.
The clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) remain dismal, with an estimated five-year survival rate of less than 5%. Early detection and prognostic approaches, including robust biomarkers for PDAC, are critical for improving patient survival. Our goal was to explore the biomarker potential of 5-hydroxymethylcytosines (5hmC), an emerging epigenetic marker with a distinct role in cancer pathobiology, yet under-investigated, due largely to technical constraints relating to PDAC. The TET-assisted bisulfite (TAB)-Array assay represents state-of-the-art technology and was used to directly profile 5hmC at single-base resolution with the Illumina EPIC array (~850,000 cytosine modification sites) in 17 pairs of tumor/adjacent tissue samples from US patients collected at the University of Chicago Medical Center. The TAB-Array data were analyzed to explore the genomic distribution of 5hmC and evaluate whether 5hmC markers were differentially modified between tumors and adjacent tissues. We demonstrated distinctive distribution patterns of 5hmC in tissue samples from PDAC patients relative to cis-regulatory elements (e.g., histone modification marks for enhancers), indicating their potential gene regulatory relevance. Substantial differences in 5hmC-modified CpG sites were detected between tumors and adjacent tissues in genes related to cancer pathobiology. The detected 5hmC-contaning marker genes also showed prognostic value for overall survival in the US patients with PDAC from the Cancer Genome Atlas Project. This study demonstrated the technical feasibility of the TAB-Array approach in cancer biomarker discovery and the biomarker potential of 5hmC for PDAC. Future studies using tissues and/or liquid biopsies may include 5hmC as a potential epigenetic biomarker target for PDAC. Full article
(This article belongs to the Special Issue The Use of Epigenetic Biomarkers as Diagnostic and Therapeutic Options)
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18 pages, 1409 KiB  
Article
Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors
by Diana L. Gerrard, Joseph R. Boyd, Gary S. Stein, Victor X. Jin and Seth Frietze
Epigenomes 2019, 3(2), 11; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3020011 - 02 Jun 2019
Cited by 11 | Viewed by 4598
Abstract
The spreading of epigenetic domains has emerged as a distinguishing epigenomic phenotype for diverse cell types. In particular, clusters of H3K27ac- and H3K4me3-marked elements, referred to as super-enhancers, and broad H3K4me3 domains, respectively, have been linked to cell identity and disease states. Here, [...] Read more.
The spreading of epigenetic domains has emerged as a distinguishing epigenomic phenotype for diverse cell types. In particular, clusters of H3K27ac- and H3K4me3-marked elements, referred to as super-enhancers, and broad H3K4me3 domains, respectively, have been linked to cell identity and disease states. Here, we characterized the broad domains from different pancreatic ductal adenocarcinoma (PDAC) cell lines that represent distinct histological grades. Our integrative genomic analysis found that human derived cell line models for distinct PDAC grades exhibit characteristic broad epigenetic features associated with gene expression patterns that are predictive of patient prognosis and provide insight into pancreatic cancer cell identity. In particular, we find that genes marked by overlapping Low-Grade broad domains correspond to an epithelial phenotype and hold potential as markers for patient stratification. We further utilize ChIP-seq to compare the effects of histone acetyltransferase (HAT) inhibitors to detect global changes in histone acetylation and methylation levels. We found that HAT inhibitors impact certain broad domains of pancreatic cancer cells. Overall, our results reveal potential roles for broad domains in cells from distinct PDAC grades and demonstrate the plasticity of particular broad epigenomic domains to epigenetic inhibitors. Full article
(This article belongs to the Special Issue The Use of Epigenetic Biomarkers as Diagnostic and Therapeutic Options)
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Review

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33 pages, 1816 KiB  
Review
A Brief Overview of lncRNAs in Endothelial Dysfunction-Associated Diseases: From Discovery to Characterization
by Rashidul Islam and Christopher Lai
Epigenomes 2019, 3(3), 20; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3030020 - 13 Sep 2019
Cited by 2 | Viewed by 3821
Abstract
Long non-coding RNAs (lncRNAs) are a novel class of regulatory RNA molecules and they are involved in many biological processes and disease developments. Several unique features of lncRNAs have been identified, such as tissue-and/or cell-specific expression pattern, which suggest that they could be [...] Read more.
Long non-coding RNAs (lncRNAs) are a novel class of regulatory RNA molecules and they are involved in many biological processes and disease developments. Several unique features of lncRNAs have been identified, such as tissue-and/or cell-specific expression pattern, which suggest that they could be potential candidates for therapeutic and diagnostic applications. More recently, the scope of lncRNA studies has been extended to endothelial biology research. Many of lncRNAs were found to be critically involved in the regulation of endothelial function and its associated disease progression. An improved understanding of endothelial biology can thus facilitate the discovery of novel biomarkers and therapeutic targets for endothelial dysfunction-associated diseases, such as abnormal angiogenesis, hypertension, diabetes, and atherosclerosis. Nevertheless, the underlying mechanism of lncRNA remains undefined in previous published studies. Therefore, in this review, we aimed to discuss the current methodologies for discovering and investigating the functions of lncRNAs and, in particular, to address the functions of selected lncRNAs in endothelial dysfunction-associated diseases. Full article
(This article belongs to the Special Issue The Use of Epigenetic Biomarkers as Diagnostic and Therapeutic Options)
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