Known epigenetic biomarkers for prostate cancer detection and management: exploring the potential of blood-based liquid biopsies

ABSTRACT

Introduction: Although prostate cancer (PCa) stands as an important cause of cancer-related deaths, a sizeable proportion of diagnosed cases are clinically insignificant. Hence, novel and more specific biomarkers to identify clinically significant PCa are needed. Liquid biopsies offer the potential to accurately identify cancer markers, including PCa. Epigenetic biomarkers such as cell-free DNA and circulating RNAs have emerged as minimally invasive cancer markers.

Areas covered: Herein, we provide an overview of epigenetic biomarkers current state based on a comprehensive review of the relevant literature in blood-based liquid biopsies and challenges/limitations of this new and growing field of cancer biomarkers.

Expert opinion: The epigenetic-based biomarkers characteristics make them attractive to the clinics and their minimally invasive assessment are a promising opportunity for PCa detection/management. The main limitations are the lack of robust validation studies and integrated approaches. Future studies would benefit from a change in focus to a ‘selected PCa detection’.

KEYWORDS:

• Biomarkers
• DNA methylation
• epigenetics
• liquid biopsy
• plasma
• prostate cancer
• serum

Article highlights

• Dealing with the widely acknowledged clinical and biological heterogeneity of prostate cancer requires an individualized approach.

• Molecular tumor profiling lies at the foundations of Precision Medicine which aims at individualized treatment based on the peculiar characteristics of each cancer in a given individual patient.

• Liquid biopsies are minimally invasive tools which allow for characterization of cancer cells genomic alterations, including epigenetic aberrations shown as promising biomarkers to improve PCa diagnosis and prognostication.

• Circulating cell-free DNA methylation and non-coding RNAs levels in bloodstream have potential clinical applications for prostate cancer detection and management.

• Considering the advantages of epigenetic biomarkers for PCa detection/prognostication and monitoring, translation into clinical practice is only hampered by the lack of robust validation studies and integrated approaches.

Declaration of interest

Rui Henrique and Carmen Jerónimo disclose a grant from Fundação para Ciência e Tecnologia - Foundation for Science and Technology, Portuguese Government. Daniela Barros-Silva holds a PhD fellowship from FCT (FCT-SFRH/BD/136007/2018). The authors declare that they have no conflict of interest to disclose. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

Research is supported by a grant from FCT (Fundação para Ciência e Tecnologia - Foundation for Science and Technology, Portuguese Government) (FCT –HyTherCaP-FCT-IC&DT-29030-COMPETE-POCI/FEDER_ 02/SAICT/2017).