Epigenetic Landscape of Liquid Biopsy in Colorectal Cancer

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.

Impact of Preanalytical and Analytical Methods on Cell-Free DNA Diagnostics

“…Biomarkers associated with different diseases have been successfully detected in cfDNA, such as copy number variations, single nucleotide polymorphisms, cfDNA integrity, and epigenetic modifications including cfDNA methylation ( Vaissière et al, 2009 ; Vaca-Paniagua et al, 2015 ; Trigg et al, 2018 ; Lee et al, 2019 ; Constâncio et al, 2020 ; Li S. et al, 2020 ; Rodriguez-Casanova et al, 2021 ; Yin et al, 2021 ). In particular cfDNA quantity, integrity, and methylation have shown themselves to be the most prominent diagnostic parameters ( Trigg et al, 2018 ; Mbaye et al, 2019 ; Lampignano et al, 2020 ; Lo et al, 2021 ; Vandekerkhove et al, 2021 ; Zhang et al, 2021 ).…”

Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma

“…In the past 10 years, a huge amount of data on epigenetic alterations in CRC has been published. Interest was placed in particular on putative clinical implications, emerging prognostic and diagnostic biomarkers, as well as on the implementation of the gained knowledge in precision (personalized) oncology [100][101][102][103][104][105].…”

Construction and Comprehensive Prognostic Analysis of a lncRNA–miRNA–mRNA Regulatory Network and Tumor Immune Cell Infiltration in Colorectal Cancer

“…At present, the common biomarkers such as kirsten rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), microsatellite stability (MSI), mismatch repair deficiency (dMMR), and carcinoembryonic antigen (CEA) were wildly used to guide clinical practice ( Koulis et al, 2020 ). In addition, epigenetic alterations are involved in CRC carcinogenesis ( Picardo et al, 2019 ; Rodriguez-Casanova et al, 2021 ). A various of genes involved epigenetic alterations were identified as potential prognostic biomarkers or therapeutic targets in recent years ( Picardo et al, 2019 ).…”