Epigenetic Biomarkers of Prostate Cancer
In contrast to gene tic changes that may vary, certain epigenetic changes are highly consistent, in particular hypermethylation of a specific set of genes, and others regularly associated with progression, such as global DNA hypomethylation, certain chromatin modifications and altered levels and composition of polycomb complexes. Although changes in polycombs and DNA methylation both accompany the progression of prostate cancer, they do not cause one another. However, they may contribute to establishing and maintaining an aberrant differentiation potential of prostate cancer initiating cells. Global DNA hypomethylation in prostate cancer may relate to adaptative changes in several signaling pathways typical of this cancer type, including innate immunity responses. Adaptative changes in the expression and function of chromatin regulators required to diminish the dependency of prostate cancer cells on androgens may shape the epigenome, beyond individual genes regulated by the androgen receptor (Schulz and Hoffmann 2009). Because of their crucial role, epigenetic biomarkers may become highly useful for diagnostics and therapy of prostate cancer.
Hypermethylated DNA can be detected in body fluids from prostate cancer patients and may be a useful biomarker, although clinical performance varies between studies. Real-time PCR was used to measure four DNA methylation biomarkers: GSTP1 and three previously unreported candidates associated with the genes RASSF2, HIST1H4K, and TFAP2E in sodium bisulfite-modified DNA (Payne et al. 2009). Analysis of all biomarkers in urine DNA significantly discriminated prostate cancer from biopsy negative patients. The biomarkers provided information independent of PSA and may warrant inclusion in nomograms for predicting prostate biopsy outcome. The biomarkers’ prostate cancer sensitivity was greater for urine than plasma DNA. The biomarker performances in urine DNA should next be validated in formal training and test studies.