Prognostic and Predictive Epigenetic Biomarkers in Oncology

Abstract

Epigenetic patterns, such as DNA methylation, histone modifications, and non-coding RNAs, can be both driver factors and characteristic features of certain malignancies. Aberrant DNA methylation can lead to silencing of crucial tumor suppressor genes or upregulation of oncogene expression. Histone modifications and chromatin spatial organization, which affect transcription, regulation of gene expression, DNA repair, and replication, have been associated with multiple tumors. Certain microRNAs (miRNAs), mainly those that silence tumor suppressor genes and occur in a greater number of copies, have also been shown to promote oncogenesis. Multiple patterns of these epigenetic factors occur specifically in certain malignancies, which allows their potential use as biomarkers. This review presents examples of tests for each group of epigenetic factors that are currently available or in development for use in early cancer detection, prediction, prognosis, and response to treatment. The availability of blood-based biomarkers is noted, as they allow sampling invasiveness to be reduced and the sampling procedure to be simplified. The article stresses the role of epigenetics as a crucial element of future cancer diagnostics and therapy.

H3K18Ac as a Marker of Cancer Progression and Potential Target of Anti-Cancer Therapy

“…The role of HATs in carcinogenesis depends on the site of acetylation of target proteins and the type of cancer [91]. Importantly, histone hypoacetylation is considered a biomarker of prognosis in many types of cancers [92].…”

ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer

“…DNA methylation is the most well-known epigenetic modification in human disease and has been implicated in regulating the expression of a great variety of genes that are critical in cancer [7]. DNA methylation status has emerged as one of the most promising epigenetic biomarkers for several types of cancer, including BC [7,8], since it can be used in early detection and prediction of prognosis or response to treatment [9,10]. For example, O-6-Methylguanine-DNA Methyltransferase (MGMT) methylation is currently used by clinicians for routine evaluation of glioma patients' therapeutic response to temozolomide [11].…”

Alternative methylation of intron motifs is associated with cancer-related gene expression in both canine mammary tumor and human breast cancer

“…Hypermethylation, which has been known to be associated with repressed gene expression of tumor suppressors, is one of the important paradigms of carcinogenesis [ 14 ] and is supported by the activated mutations of DNA methyltransferases (DNMTs) being oncogenic in several tissues [ 15 ]. In various human cancers, genome-wide methylation has been profiled [ 14 ] and global DNA hypomethylation [ 16 ], along with local hyper- (tumor suppressors) and hypo- (oncogenes) methylations concomitant with the respective silencing and activating of gene expression [ 17 , 18 ] were reported and suggested as potential diagnostic and predictive biomarkers [ 19 ]. The use of methylation alteration as a biomarker has several obvious advantages, such as early detection and relative specimen stability, but only a few are currently clinically used (e.g., methylation of MGMT in glioblastoma, SEPT9 in hepatocellular carcinoma, and PITX2 in breast cancer) [ 20 ].…”