Abstract
Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential.RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1andTIG1were highly methylated in PCa compared to BPH (p < 0.001), whileSERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2aandSFNwere not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level ofSFN, SLIT2andSERPINB5distinguished low and high Gleason score cancers, e.g.SFNandSERPINB5together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes includingCDH1previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001).Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes likeRARB, HIN1, BCL2, APC and GSTP1is warranted for diagnostic potential andSFN, SLIT2andSERPINB5for prognostic potential.
Highlights
Prostate cancer (PCa) is one of the most common malignancies affecting men and is a major public health problem likely to increase in magnitude with an increasingly aged population
Other than Prostate specific antigen (PSA), with all its limitations, no generally accepted validated biomarkers are currently available for prognosis or therapeutic prediction in prostate cancer
TMPRSS-ERG [45], Ki-67 [46], HSP27 [47] and others are under consideration, they are not validated for widespread use and Gleason score and PSA in the context of other clinical information remain the mainstay of decision making in PCa [24]
Summary
Prostate cancer (PCa) is one of the most common malignancies affecting men and is a major public health problem likely to increase in magnitude with an increasingly aged population. Prostate specific antigen (PSA) screening for PCa is widely used in the USA, which has the highest reported incidence worldwide [1]. PSA is valuable for early detection of PCa. The anticipated wider adoption of PSA screening in Europe will lead to increases in reported incidence of PCa, possibly reaching levels seen in the USA. While PSA screening decreases the absolute risk of death from PCa, the lives saved come at a price of invasive examinations and biopsy of healthy men, risk of over-diagnosis and over-treatment as well as increased health care burden [2,3]. It is estimated that to save one life, 1410 men need to be screened
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
