Abstract
Colorectal cancer (CRC) is one of the most common malignancies and is a major cause of cancer-related deaths worldwide. Thus, there is a clinical need to improve early detection of CRC and personalize therapy for patients with this disease. In the era of precision oncology, liquid biopsy has emerged as a major approach to characterize the circulating tumor elements present in body fluids, including cell-free DNA and RNA, circulating tumor cells, and extracellular vesicles. This non-invasive tool has allowed the identification of relevant molecular alterations in CRC patients, including some indicating the disruption of epigenetic mechanisms. Epigenetic alterations found in solid and liquid biopsies have shown great utility as biomarkers for early detection, prognosis, monitoring, and evaluation of therapeutic response in CRC patients. Here, we summarize current knowledge of the most relevant epigenetic mechanisms associated with cancer development and progression, and the implications of their deregulation in cancer cells and liquid biopsy of CRC patients. In particular, we describe the methodologies used to analyze these epigenetic alterations in circulating tumor material, and we focus on the clinical utility of epigenetic marks in liquid biopsy as tumor biomarkers for CRC patients. We also discuss the great challenges and emerging opportunities of this field for the diagnosis and personalized management of CRC patients.
Highlights
Colorectal cancer (CRC) is the third most frequently detected cancer in both sexes worldwide
This study revealed that circulating tumor cells (CTCs) from CRC patients are characterized by hypermethylation of the SFRP2 promoter and exon 1 of VIM (Lyberopoulou et al, 2017), which are genes related to epithelial-to-mesenchymal transition (EMT) and CRC metastasis (Shirahata et al, 2009; Loboda et al, 2011; Vincent and Postovit, 2017)
The interest in epigenetic alterations associated with CRC development and progression as potential clinical biomarkers or therapeutic targets has increased significantly in recent years
Summary
Colorectal cancer (CRC) is the third most frequently detected cancer in both sexes worldwide. Liquid biopsy has emerged in recent years as an important approach to address and overcome such limitations This non-invasive strategy allows to observe the molecular landscape of circulating tumor elements in body fluids to obtain diagnostic, prognostic, and therapy response biomarkers that improve the management of cancer patients (Siravegna et al, 2017). The analysis of these liquid biopsy components in several body fluids of CRC patients has highlighted relevant molecular alterations, such as those depending on epigenetic mechanisms (Lofton-Day et al, 2008; Maminezhad et al, 2020). The disruption of ncRNA expression in cancer cells may alter histone PTMs and DNA methylation levels (Gupta et al, 2010)
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