DNA Methylation-Based Testing in Liquid Biopsies as Detection and Prognostic Biomarkers for the Four Major Cancer Types

Abstract

Lung, breast, colorectal, and prostate cancers are the most incident worldwide. Optimal population-based cancer screening methods remain an unmet need, since cancer detection at early stages increases the prospects of successful and curative treatment, leading to a lower incidence of recurrences. Moreover, the current parameters for cancer patients’ stratification have been associated with divergent outcomes. Therefore, new biomarkers that could aid in cancer detection and prognosis, preferably detected by minimally invasive methods are of major importance. Aberrant DNA methylation is an early event in cancer development and may be detected in circulating cell-free DNA (ccfDNA), constituting a valuable cancer biomarker. Furthermore, DNA methylation is a stable alteration that can be easily and rapidly quantified by methylation-specific PCR methods. Thus, the main goal of this review is to provide an overview of the most important studies that report methylation biomarkers for the detection and prognosis of the four major cancers after a critical analysis of the available literature. DNA methylation-based biomarkers show promise for cancer detection and management, with some studies describing a “PanCancer” detection approach for the simultaneous detection of several cancer types. Nonetheless, DNA methylation biomarkers still lack large-scale validation, precluding implementation in clinical practice.

Hypermethylation of tumor necrosis factor decoy receptor gene in non‑small lung cancer

“…However, tissue biopsy is inconvenient and traumatic. Liquid biopsy, such as circulating tumor cells, circulating tumor DNA and exosomes can provide more comprehensive disease information (42,43). Furthermore, investigating the methylation levels of TNFRSF10C and TNFRSF10D genes of patients' blood samples, and combining data from both tissues and blood may allow their development as novel diagnostic biomarkers of lung cancer.…”

Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

“…Progressive gains of promoter methylation resulting in silencing of tumor suppressor genes and global hypomethylation associated with genome instability have been extensively reported in BC [67,68]. Locus-specific aberrant DNA methylation patterns were correlated with several clinical, molecular, and pathological features, including the status of the protein p53, histological stage, and prognosis [69,70]. Hypermethylation of the BRCA1 gene was associated with ER (estrogen receptor)-negative breast tumors and poor clinical outcome [71].…”

Comprehensive analysis of DNA methylation and gene expression profiles in rectal cancer

“…Therefore, CpG islands are generally methylated in promoters of silencing genes and not methylated in transcriptionally active genes [13] . Furthermore, abnormal hypomethylation of oncogenes and hypermethylation of tumor suppressor genes have been found to play important roles in human tumorigenesis and cancer progression, including those of RC [14][15][16] . For example, Ye et al [17] performed whole-exome sequencing in 50 RC patients and found pervasive decreased expression of PCDHB3 due to CpG island hypermethylation.…”