Abstract
BACKGROUND. Prostate cancer (PCa) is the second most prevalent malignancy among males, characterized by high mortality rates. Aberrant DNA methylation in promoters of tumor suppressor genes is an early and frequent event during prostate carcinogenesis. Modern techniques allow a sensitive detection of DNA methylation biomarkers in bodily fluids from cancer patients offering a noninvasive tool for PCa monitoring. Our study aimed at the analysis of DNA methylation in urine sediments from PCa patients for the selection of most informative noninvasive biomarkers. MATERIAL AND METHODS. Real-time methylation-specific polymerase chain reaction was used for the detection of methylated RASSF1, RARB, and GSTP1 genes in catheterized urine specimens from 34 patients with biopsy-proven early or medium stage PCa. RESULTS. At least one gene was methylated in urine sediments from 28 cases with PCa, with a sensitivity of the test reaching 82%. RASSF1 was methylated in 71% (24 of 34), RARB in 44% (15 of 34), and GSTP1 in 3% (1 of 34) of the specimens. High level of methylation (≥50%) in RARB and RASSF1 genes was detected in 40% and 20% of cases, respectively. A significant association was observed between high level of RARB methylation and Gleason score (P=0.01), while methylation of at least one gene occurred more frequently in urine DNA of older patients (P=0.02). CONCLUSIONS. Results of our study show a high sensitivity of DNA methylation biomarkers, especially RASSF1 and RARB, for the early and noninvasive detection of PCa.
Highlights
Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of death from cancer among men worldwide [1]
Results of our study show a high sensitivity of DNA methylation biomarkers, especially RASSF1 and RARB, for the early and noninvasive detection of PCa
RASSF1, gene of interest; myogenic differentiation gene 1 (MYOD1), reference gene used to normalize for DNA input; NTC, nontemplate control; MC, in vitro fully methylated leukocyte DNA used as a positive control; S8, sample of urine sediments; horizontal solid line, amplification-based threshold
Summary
Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of death from cancer among men worldwide [1]. In 2009, more than 3000 new cases of PCa were diagnosed in Lithuania. In our country, it is the most prevalent cancer and the second leading cause of death among men [2]. When the level of PSA is increased, prostate biopsy is recommended, with 4 ng/mL of PSA being the usual threshold level. This protein is specific for prostate tissue, but not for PCa. this protein is specific for prostate tissue, but not for PCa Such noncancerous conditions as benign prostatic hyperplasia (BPH), prostatitis, or prostatic ischemia can cause the elevated levels of PSA [1, 4]. The development of a minimally invasive, yet specific, tool to aid in the early detection of PCa is needed
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