MiR-182-5p and miR-375-3p Have Higher Performance Than PSA in Discriminating Prostate Cancer from Benign Prostate Hyperplasia

SIMPLE SUMMARY: Prostate cancer (PCa) is the most prevalent neoplasia among men worldwide but is commonly “mimicked” by benign prostate hyperplasia (BPH). Their discrimination by the prostate-specific antigen (PSA) is often uncertain, resulting in lengthy diagnostic protocols and recurrent tissue biopsies. The development of more appropriate biomarkers, possibly present in liquid biopsy, would significantly improve PCa and BPH patient management. To address this challenge, in this study miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were analyzed by ddPCR in blood plasma and seminal plasma of patients with PCa and BPH prior to tissue biopsy. Among other findings, miR-182-5p and miR-375-3p were found to have statistically significantly higher expression in PCa patients compared to BPH in blood, with a combined specificity of 90.2% to predict positive or negative biopsy results. The data presented emphasize the great potential of miRNAs as liquid biopsy biomarkers for PCa. ABSTRACT: Prostate cancer (PCa) is the most commonly diagnosed neoplasm among men. Since it often resembles benign prostate hyperplasia (BPH), biomarkers with a higher differential value than PSA are required. Epigenetic biomarkers in liquid biopsies, especially miRNA, could address this challenge. The absolute expression of miR-375-3p, miR-182-5p, miR-21-5p, and miR-148a-3p were quantified in blood plasma and seminal plasma of 65 PCa and 58 BPH patients by digital droplet PCR. The sensitivity and specificity of these microRNAs were determined using ROC curve analysis. The higher expression of miR-182-5p and miR-375-3p in the blood plasma of PCa patients was statistically significant as compared to BPH (p = 0.0363 and 0.0226, respectively). Their combination achieved a specificity of 90.2% for predicting positive or negative biopsy results, while PSA cut-off of 4 µg/L performed with only 1.7% specificity. In seminal plasma, miR-375-3p, miR-182-5p, and miR-21-5p showed a statistically significantly higher expression in PCa patients with PSA >10 µg/L compared to ones with PSA ≤10 µg/L. MiR-182-5p and miR-375-3p in blood plasma show higher performance than PSA in discriminating PCa from BPH. Seminal plasma requires further investigation as it represents an obvious source for PCa biomarker identification.