Year-end Sale % OFF 
Abstract
BackgroundProstate cancer (PCa) is one of the most common cancers among men worldwide. Current screening methods for PCa display limited sensitivity and specificity, not stratifying for disease aggressiveness. Hence, development and validation of new molecular markers is needed. Aberrant gene promoter methylation is common in PCa and has shown promise as clinical biomarker. Herein, we assessed and compared the diagnostic and prognostic performance of two-gene panel promoter methylation in the same sample sets.MethodsPromoter methylation of panel #1 (singleplex-miR-34b/c and miR-193b) and panel #2 (multiplex-APC, GSTP1, and RARβ2) was evaluated using MethyLight methodology in two different cohorts [prostate biopsy (#1) and urine sediment (#2)]. Biomarkers’ diagnostic (validity estimates) and prognostic (disease-specific survival, disease-free survival, and progression-free survival) performance was assessed.ResultsPromoter methylation levels of both panels showed the highest levels in PCa samples in both cohorts. In tissue samples, methylation panel #1 and panel #2 detected PCa with AUC of 0.9775 and 1.0, respectively, whereas in urine samples, panel #2 demonstrated superior performance although a combination of miR-34b/c, miR-193b, APC, and RARβ2 disclosed the best results (AUC = 0.9817). Furthermore, higher mir-34b/c and panel #2 methylation independently predicted for shorter DSS. Furthermore, time-dependent ROC curves showed that both miR-34b/c and GSTP1 methylation levels identify with impressive performance patients that relapse up to 15 years after diagnosis (AUC = 0.751 and AUC = 0.765, respectively).ConclusionsWe concluded that quantitative gene panel promoter methylation might be a clinically useful tool for PCa non-invasive detection and risk stratification for disease aggressiveness in both tissue biopsies and urines.
Highlights
Prostate cancer (PCa) is one of the most common cancers among men worldwide
Diagnostic performance of genes’ promoter methylation in prostate biopsy and urine sediments using different panels To determine the performance of the gene methylation panels as PCa detection tools, receiver operator characteristics (ROC) curve analysis was carried out and an empirical cutoff value was defined for calculation of biomarker performance (Additional file 1: Tables S3 and S4)
In prostate biopsy, methylation levels of all gene promoters were significantly higher in PCa patients compared to controls (Additional file 2: Figure S1)
Summary
Prostate cancer (PCa) is one of the most common cancers among men worldwide. Current screening methods for PCa display limited sensitivity and specificity, not stratifying for disease aggressiveness. Aberrant gene promoter methylation is common in PCa and has shown promise as clinical biomarker. Prostate cancer (PCa) remains a major public health concern in male gender mainly due to increased life expectancy and population aging [1]. This neoplasm is usually clinically silent until extra-prostatic invasion or metastatic occurs, entailing the need for development and implementation of effective screening methods that allow for detection of PCa while still confined to the prostate, at a potentially curable stage. Notwithstanding recent advances in characterization of PCa biology, significant challenges concerning adequate PCa management remain, as new stratification methods and its clinical validation are still needed [4]. DNA methylation alterations are sufficiently stable and quantifiable in liquid biopsies [8, 9], which constitute a valuable and minimally invasive means of interrogating the presence of tumor cell DNA in bodily fluids
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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.
