Current prostate carcinoma (PCa) biomarkers, including total prostate-specific antigen (tPSA), have unsatisfactory diagnostic sensitivity and specificity resulting in overdiagnosis and overtreatment. Previously, we described an optimised bias-based preamplification–digital droplet PCR (OBBPA-ddPCR) technique, which detects tumour DNA in blood-derived cell-free DNA (cfDNA) of cancer patients. The current study investigated the performance of newly developed OBBPA-ddPCR-based biomarkers. Blood plasma samples from healthy individuals (n= 90, controls) and PCa (n= 39) and benign prostatic hyperplasia patients (BPH,n= 40) were analysed. PCa and BPH patients had tPSA values within a diagnostic grey area of 2–15 ng/mL, for whom further diagnostic validation is most crucial. Methylation levels of biomarkersRASSF1A,MIR129-2,NRIP3, andSOX8were found significantly increased in PCa patients compared to controls. By combining classical PCa risk factors (percentage of free PSA compared to tPSA (QfPSA) and patient’s age) with cfDNA-based biomarkers, we developed PCa risk scores with improved sensitivity and specificity compared to established tPSA and QfPSA single-marker analyses. The diagnostic specificity was increased to 70% with 100% sensitivity for clinically significant PCa patients. Thus, prostate biopsies could be avoided for 28 out of 40 BPH patients. In conclusion, the newly developed risk scores may help to confirm the clinical decision and prevent unnecessary prostate biopsy.
目前的前列腺癌（PCa）生物标志物，包括总前列腺特异性抗原（tPSA），其诊断敏感性和特异性均不理想，导致过度诊断和过度治疗。此前，我们描述了一种优化的基于偏倚的预扩增-数字液滴PCR（OBBPA-ddPCR）技术，该技术可检测癌症患者血液来源的游离DNA（cfDNA）中的肿瘤DNA。本研究评估了新开发的基于OBBPA-ddPCR的生物标志物的性能。我们分析了健康个体（n=90，对照组）、PCa患者（n=39）和良性前列腺增生患者（BPH，n=40）的血浆样本。PCa和BPH患者的tPSA值均处于2-15 ng/mL的诊断灰色区域，对于这部分患者，进一步的诊断验证至关重要。研究发现，与对照组相比，PCa患者中生物标志物RASSF1A、MIR129-2、NRIP3和SOX8的甲基化水平显著升高。通过将经典的PCa风险因素（游离PSA与tPSA的百分比（QfPSA）和患者年龄）与基于cfDNA的生物标志物相结合，我们开发了PCa风险评分，与现有的tPSA和QfPSA单一标志物分析相比，其敏感性和特异性均有所提高。对于具有临床意义的PCa患者，诊断特异性提高至70%，同时保持100%的敏感性。因此，40名BPH患者中有28名可避免前列腺活检。总之，新开发的风险评分可能有助于确认临床决策并避免不必要的前列腺活检。
肿瘤(癌症)患者之家