Epigenetics of colorectal cancer: emerging circulating diagnostic and prognostic biomarkers

Colorectal cancer (CRC) is one of the most common cancers worldwide and the second leading cause of cancer-related mortality in western countries. Despite the high incidence, treatment options for advanced CRC remain limited and unsuccessful, resulting in a poor prognosis. Therefore, novel accurate diagnostic, prognostic and predictive biomarkers are clearly and urgently needed to detect advanced colon polyps and early stage CRC and to identify the most effective treatments for specific CRC patients. CRC is known to develop from early premalignant lesions to full blown cancer via a multi-step process involving a series of genetic mutations that accumulate over time. Recent improvement of our understanding of CRC biology and advances in genomic technologies has led to the identification of a variety of epigenetic alterations strongly involved in cancer initiation and progression. Among the epigenetic marks implicated in CRC the most widely studied are the global DNA hypomethylation, the promoter hypermethylation and the miRNAs dysregulations. Many evidence exist that such tumour associated alterations may serve as new potential biomarkers. Moreover, due the non-invasive, objective, and potential reproducible assessment, circulating epigenetic biomarkers have reached increasing attentions in the last few years. In this review, we attempt to analyze the existing most recent literature on the role of circulating DNA methylations and miRNAs alterations in CRC diagnosis and prognosis.