Promoter Hypermethylation as a Biomarker in Prostate Adenocarcinoma

Abstract

There is increasing evidence that DNA methylation is a critical source of gene regulation. In addition, interindividual differences in DNA methylation status in cancer related genes are associated with risk and progression of prostate cancer. Therefore, DNA methylation in cancer related genes can be potential biomarkers and therapeutic targets for prostate cancer.In this chapter, current information on frequently hypermethylated genes associated with the carcinogenesis and progression of prostate cancer was updated. The potential biological role of hypermethylated genes in prostate cancer is discussed. These findings may provide new information of the pathogenesis, the exciting potential to be predictive and to provide strategies for personalized treatment of prostate cancer.

Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies

“…Promoter hypermethylation is closely associated with gene silencing and may cause downregulation of, for example, tumor suppressor genes during carcinogenesis (Kulis and Esteller, ; Wu et al ., ). Moreover, aberrant promoter hypermethylation of specific genes has been reported to hold promising diagnostic and/or prognostic biomarker potential for PC in tissue samples (Park, ; Sorensen et al ., , ; Strand et al ., ). Furthermore, hypermethylation of circulating tumor DNA (ctDNA), which is shed from tumors into the bloodstream as a result of apoptosis, necrosis, and/or active secretion, can be detected in liquid biopsies (plasma/serum) from patients with PC (Polivka et al ., ), suggesting a promising potential for development of noninvasive or minimally invasive diagnostic tests.…”

Comprehensive Evaluation of TFF3 Promoter Hypomethylation and Molecular Biomarker Potential for Prostate Cancer Diagnosis and Prognosis

“…Some of the genes affected by perturbed promoter methylation levels are potential tumor suppressors or drivers of PC, as their transcriptional expression is repressed or activated upon promoter hyper- or hypomethylation, respectively [ 4 ]. In recent years, several candidate promoter hypermethylation markers for PC diagnosis have been identified [ 5 , 6 , 7 , 8 , 9 , 10 ], some of which have also shown promising prognostic potential for prediction of prostate-specific antigen (PSA) recurrence after RP [ 5 , 6 , 8 , 11 , 12 , 13 , 14 ]. Likewise, aberrant promoter hypomethylation has been proposed as a cancer biomarker in, e.g., myelofibrosis [ 15 ] and glioma [ 16 ], but it has not been extensively studied for PC.…”

Large‐scale evaluation of SLC18A2 in prostate cancer reveals diagnostic and prognostic biomarker potential at three molecular levels

“…A subset of these genes show reduced mRNA expression upon DNA methylation, and hence are potential drivers of cancer development (Sproul et al, 2012) and often considered candidate tumor suppressors (Yang and Park, 2012). Candidate DNA methylation markers for prostate cancer have been reported to be hypermethylated in 70e100% of prostate cancer samples (Ahmed, 2010;Haldrup et al, 2013;Kristensen et al, 2014;Park, 2015), and are thus highly attractive for diagnostic applications. In addition, a few candidate DNA methylation markers have demonstrated promising prognostic value for prediction of PSA recurrence after RP (Banez et al, 2010;Haldrup et al, 2013;Kristensen et al, 2014;Schatz et al, 2010;Strand et al, 2014;Weiss et al, 2009).…”