Identification of aberrant DNA methylation is a promising tool in prostate cancer (PCa) diagnosis and treatment. In this study, we evaluated a two-step method named optimised bias-based preamplification followed by digital PCR (OBBPA-dPCR). The method was used to identify promoter hypermethylation of 2 tumour suppressor genes and in the circulating cell-free DNA (cfDNA) from serum samples of PCa patients ( = 75), benign prostatic hyperplasia (BPH, = 58), and healthy individuals (controls, = 155). The PCa cohort was further subdivided into subgroups comprising (I) patients with Gleason Scores (GS) ≤ 7 ( = 55), (II) GS ≥ 8 ( = 10), and (III) patients with metastatic PCa diagnosis ( = 10). We found that methylation levels were significantly increased in all 3 PCa subgroups compared to the controls and BPH cohorts ( < 0.01 for all comparisons). Fractional abundances of methylated DNA fragments were significantly increased in subgroup III of metastatic PCa patients ( < 0.001). methylation analysis was found to be beneficial as a complementary biomarker where further diagnostic validation is most crucial. In combination with free PSA, methylation status helps to identify PCa patients with GS ≥ 8 and grey-zone total PSA values between 2-10 ng/mL. In our study, PCR biases between 80-90% were sufficient to detect minute amounts of tumour DNA with high signal-to-noise ratios as well as high analytical sensitivity and specificity. Both and exhibited strongly increased DNA methylation levels in all metastatic PCa patients. Our data indicates a superior sensitivity of epigenetic biomarker analyses in early detection of PCa metastases that should also help to improve PCa therapy.
About The Expert
Manfred P Wirth