DNA methylation and microRNA biomarkers for noninvasive detection of gastric and colorectal cancer

Cancer initiation and progression is controlled by both genetic and epigenetic events. Epigenetics refers to the study of mechanisms that alter gene expression without permanently altering the DNA sequence. Epigenetic alterations are reversible and heritable, and include changes in histone modifications, DNA methylation, and non-coding RNA-mediated gene silencing. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Aberrant epigenetic modifications occur at the earliest stages of neoplastic transformation and are now believed to be essential players in cancer initiation and progression. Recent advances in epigenetics have not only offered a deeper understanding of the underlying mechanism(s) of carcinogenesis, but have also allowed identification of clinically relevant putative biomarkers for the early detection, disease monitoring, prognosis and risk assessment of cancer patients. At this moment, DNA methylation and non-coding RNA including with microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) represent the largest body of available literature on epigenetic biomarkers with the highest potential for cancer diagnosis. Following identification of cell-free nucleic acids in systematic circulation, increasing evidence has demonstrated the potential of cell-free epigenetic biomarkers in the blood or other body fluids for cancer detection. In this article, we summarize the current state of knowledge on epigenetic biomarkers - primarily DNA methylation and non-coding RNAs - as potential substrates for cancer detection in gastric and colorectal cancer, the two most frequent cancers within the gastrointestinal tract. We also discuss the obstacles that have limited the routine use of epigenetic biomarkers in the clinical settings and provide our perspective on approaches that might help overcome these hurdles, so that these biomarkers can be readily developed for clinical management of cancer patients. (C) 2014 Elsevier Inc. All rights reserved.