An update of aberrant methylation detection on circulating cell-free DNA as a tool to improve prostate cancer diagnosis and prognosis

Abstract

Prostate cancer (PCa) remains a disease of high incidence, but orphan of a specific screening program. For this reason, non-invasive techniques capable to predict PCa in patients with high specificity and sensitivity are still an urgent need. One of the major goals is to improve the PCa diagnosis and the identification of patients who benefit from tissue biopsies. Another need is the necessity to have novel biomarkers to better stratify the risk of patients with PCa to predict the aggressiveness of the tumor and the overall survival. Liquid biopsy can be an important non-invasive tool to stratify PCa at the molecular level to improve diagnosis and prognosis, and, possibly, to develop screening programs and follow-up. With this review, we are reporting the lastest update of aberrant methylation detection on circulating tumor DNA as a tool to improve prostate cancer diagnosis and prognosis.

Keywords

Liquid biopsy / DNA / methylation / prostate cancer / cfDNA / ctDNA / biomarker

References

[1] SiegelRL,JemalA.Cancer statistics, 2019.CA Cancer J Clin2018;69:7-34

[2] GoeringW,SchulzWA. DNA methylation changes in prostate cancer. In: Dumitrescu RG, Verma M, editors. Cancer epigenetics. Totowa: Humana Press; 2012. p. 47-66.

[3] SobhaniN,GeneraliD,ScaggianteB.Circulating cell-free nucleic acids as prognostic and therapy predictive tools for metastatic castrate-resistant prostate cancer.World J Clin Oncol2020;11:450-63 PMCID:PMC7407926

[4] BrikunI,FreijeD.An expanded biomarker panel for the detection of prostate cancer from urine DNA.Exp Hematol Oncol2019;8:13 PMCID:PMC6598372

[5] BrikunI,DecatusA,LiL.A panel of DNA methylation markers for the detection of prostate cancer from FV and DRE urine DNA.Clin Epigenetics2018;10:91 PMCID:PMC6029393

[6] NekrasovKA,RudenkoEE.6-gene promoter methylation assay is potentially applicable for prostate cancer clinical staging based on urine collection following prostatic massage.Oncol Lett2019;18:6917-25 PMCID:PMC6876302

[7] ConnellSP,TuzovaA.Development of a multivariable risk model integrating urinary cell DNA methylation and cell-free RNA data for the detection of significant prostate cancer.Prostate2020;80:547-58 PMCID:PMC7383590

[8] ZhaoF,LiuRSC.Combining urinary DNA methylation and cell-free microRNA biomarkers for improved monitoring of prostate cancer patients on active surveillance.Urol Oncol2019;37:297.e9-297.e17

[9] SilvaR,RussellNM.Evaluating liquid biopsies for methylomic profiling of prostate cancer.Epigenetics2020;15:715-27 PMCID:PMC7574384

[10] HaldrupC,ØgaardN.Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies.Mol Oncol2018;12:545-60 PMCID:PMC5891052

[11] ReisIM,SpeerC,SingalR.Serum GADD45a methylation is a useful biomarker to distinguish benign vs malignant prostate disease.Br J Cancer2015;113:460-8 PMCID:PMC4522641

[12] ConstâncioV,Moreira-BarbosaC.Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel.Clin Epigenetics2019;11:175 PMCID:PMC6889617

[13] MenschikowskiM,FriedemannM.Identification of rare levels of methylated tumor DNA fragments using an optimized bias based pre-amplification-digital droplet PCR (OBBPA-ddPCR).Oncotarget2018;9:36137-50 PMCID:PMC6281424

[14] BjerreMT,LarsenOH.Epigenetic analysis of circulating tumor DNA in localized and metastatic prostate cancer: evaluation of clinical biomarker potential.Cells2020;9:1362 PMCID:PMC7349912

[15] BeltranH,ConteducaV.Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer.J Clin Invest2020;130:1653-68 PMCID:PMC7108892

[16] O'ReillyE,WalshAL.epiCaPture: a urine DNA methylation test for early detection of aggressive prostate cancer.JCO Precis Oncol2019;2019:PO.18.00134 PMCID:PMC6383793

[17] CarsonJJK,BermanDM,MuellerCR.Development and initial clinical correlation of a DNA methylation-based blood test for prostate cancer.Prostate2020;80:1038-42

[18] WuA,WetterskogD.Genome-wide plasma DNA methylation features of metastatic prostate cancer.J Clin Invest2020;130:1991-2000 PMCID:PMC7108919