Bridging the Gaps between Circulating Tumor Cells and DNA Methylation in Prostate Cancer

Abstract

Prostate cancer is the second most common male malignancy, with a highly variable clinical presentation and outcome. Therefore, diagnosis, prognostication, and management remain a challenge, as available clinical, imaging, and pathological parameters provide limited risk assessment. Thus, many biomarkers are under study to fill this critical gap, some of them based on epigenetic aberrations that might be detected in liquid biopsies. Herein, we provide a critical review of published data on the usefulness of DNA methylation and circulating tumor cells in diagnosis and treatment decisions in cases of prostate cancer, underlining key aspects and discussing the importance of these advances to the improvement of the management of prostate cancer patients. Using minimally invasive blood tests, the detection of highly specific biomarkers might be crucial for making therapeutic decisions, determining response to specific treatments, and allowing early diagnosis.

Keywords: DNA methylation; circulating tumor cells; prostate cancer.

Figure 1

CTC enrichment methods and characterization. CTCs can be enriched on the basis of their physical or biological properties, such as size, density, electrical charge, antibodies, and/or the use of microfluidic devices. After enrichment, several methods can be applied to characterize the various subgroups of CTCs, using well-known technologies, including methylation analysis of target genes. CTC: Circulating Tumor Cell; EVs: Extracellular Vesicles.

Figure 2

Relevant hypermethylated genes in prostate CTCs. Methylation is characterized by the addition of a covalent methyl group. This mechanism is catalyzed by DNA methyltransferase enzymes (DNMTs), while TET proteins promote a locus-specific reversal effect of DNA methylation. Herein, the targets already found to be hypermethylated in prostate CTCs are also represented.