Abstract
Simple SummaryProstate cancer is a major cause of cancer-related death in men worldwide. There is an urgent clinical need for improved prognostic biomarkers to better predict the likely outcome and course of the disease and thus inform the clinical management of these patients. Currently, clinically recognised prognostic markers lack sensitivity and specificity in distinguishing aggressive from indolent disease, particularly in patients with localised, intermediate grade prostate cancer. Thus, there is major interest in identifying new molecular biomarkers to complement existing standard clinicopathological markers. DNA methylation is a frequent alteration in the cancer genome and offers potential as a reliable and robust biomarker. In this review, we provide a comprehensive overview of the current state of DNA methylation biomarker studies in prostate cancer prognosis. We highlight advances in this field that have enabled the discovery of novel prognostic genes and discuss the potential of methylation biomarkers for noninvasive liquid-biopsy testing.There is a major clinical need for accurate biomarkers for prostate cancer prognosis, to better inform treatment strategies and disease monitoring. Current clinically recognised prognostic factors, including prostate-specific antigen (PSA) levels, lack sensitivity and specificity in distinguishing aggressive from indolent disease, particularly in patients with localised intermediate grade prostate cancer. There has therefore been a major focus on identifying molecular biomarkers that can add prognostic value to existing markers, including investigation of DNA methylation, which has a known role in tumorigenesis. In this review, we will provide a comprehensive overview of the current state of DNA methylation biomarker studies in prostate cancer prognosis, and highlight the advances that have been made in this field. We cover the numerous studies into well-established candidate genes, and explore the technological transition that has enabled hypothesis-free genome-wide studies and the subsequent discovery of novel prognostic genes.
Highlights
Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer in men and one of the leading causes of cancer death in males
The earliest of these studies assessed GSTP1 methylation using quantitative methylation-specific PCR (qMSP) in a cohort of GS 7 (3 + 4) patients (n = 74), and reported that GSTP1 hypermethylation was significantly associated with time to progression in univariate analysis, and as an independent predictor in multivariate analysis with other candidate genes [75]
Of the genes included in the panel, GSTP1 has been widely studied as a diagnostic and prognostic biomarker of PCa [44,45,144], whilst GRASP and TPM4 have been previously shown to be differentially methylated in PCa compared to normal prostate tissue [132]
Summary
Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer in men and one of the leading causes of cancer death in males. RP represents an overtreatment given the risk of unnecessary side effects and compromised quality of of life [17,18] Strategies such as as have emerged forformen men diagnosed with low disease, grade disease, in regular which monitoring regular monitoring is detect used to detectprogression, tumour diagnosed with low grade in which is used to tumour progression, with the aim of delaying until it is clinically necessary [19]. The ability to identify initial diagnosis would inform decisions about personalized treatment and/or monitoring strategies, the risk of progression at initial diagnosis would inform decisions about personalized treatment as well as the use of adjuvant therapy, for improved clinical management and enhanced outcomes and/or monitoring strategies, as well as the use of adjuvant therapy, for improved clinical for PCa patients
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