Epigenetic Biomarkers for the Early Detection of Gastrointestinal Cancer

Gastric cancer and colorectal cancer, the two most frequent cancers within the gastrointestinal tract, account for a large proportion of human malignancies worldwide. The initiation and progression of gastrointestinal cancer (GIC) is controlled by both genetic and epigenetic events. Epigenetic alterations, including changes in DNA methylation, specific histone modifications, chromatin remodeling and noncoding RNA-mediated gene silencing, are potentially reversible and heritable.

In this article, we summarize the current advances in epigenetic biomarkers as potential substrates for GIC detection. The combined screening of a panel of methylated genes, hyperacetylated histones, microRNAs or other noncoding RNAs is currently under evaluation to improve sensitivity.

Current studies concentrated on the development of cost-effective epigenetic diagnostic biomarkers for GIC based on noninvasive blood or stool samples. The combined blood or stool test with a relatively high sensitivity could be a cost-effective screening tool for the detection of patients with asymptomatic cancers who could therefore choose whether or not to go for further examinations, such as endoscopy or colonoscopy.

A better understanding of epigenetic mechanisms has not only offered new insights into a deeper understanding of the underlying mechanisms of carcinogenesis, but has also allowed identification of clinically relevant putative biomarkers for the early detection, disease monitoring, prognosis and risk assessment of GIC. In particular, noninvasive biomarkers in serum or fecal samples for the detection of GIC could have potential for better compliance and can be incorporated into routine clinical practice in the foreseeable future, pending their validation in large-scale prospective trials.