title: Prognostic DNA methylation markers for prostate cancer.
abstract: Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. Siri.Strand@clin.au.dk.
authors.forename: Siri H
authors.initials: SH
authors.lastname: Strand
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. Orntoft@clin.au.dk.
authors.forename: Torben F
authors.initials: TF
authors.lastname: Orntoft
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. kdso@clin.au.dk.
authors.forename: Karina D
authors.initials: KD
authors.lastname: Sorensen
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000401:mortality; D015415:Biomarkers; D001826:Body Fluids / Q000737:chemistry; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D055088:Early Detection of Cancer; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008868:Microtubule Proteins; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality; D011506:Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics*
chemical_list: D015415:Biomarkers; C000598176:CCDC181 protein, human; D004273:DNA, Neoplasm; C546140:MIRN224 microRNA, human; C574051:MIRN452 microRNA, human; D035683:MicroRNAs; D008868:Microtubule Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012334:RNA, Neoplasm