Combinations of Serum Prostate-Specific Antigen and Plasma Expression Levels of let-7c, miR-30c, miR-141, and miR-375 as Potential Better Diagnostic Biomarkers for Prostate Cancer

In the current study, expression levels of let-7c, miR-30c, miR-141, and miR-375 in plasma from 59 prostate cancer (PC) patients with different clinicopathological characteristics and two groups of controls: 16 benign prostatic hyperplasia (BPH) samples and 11 young asymptomatic men (YAM) were analyzed to evaluate their diagnostic and prognostic value in comparison to prostate-specific antigen (PSA). miR-375 was significantly downregulated in 83.5% of patients compared to BPH controls and showed stronger diagnostic accuracy (area under the curve [AUC]=0.809, 95% CI: 0.697-0.922, p=0.00016) compared with PSA (AUC=0.710, 95% CI: 0.559-0.861, p=0.013). Expression levels of let-7c showed potential to distinguish PC patients from BPH controls with AUC=0.757, but the result did not reach significance. Better discriminating performance was observed when combinations of studied biomarkers were used. Sensitivity of 86.8% and specificity of 81.8% were reached when all biomarkers were combined (AUC=0.877) and YAM were used as calibrators. None of the studied microRNAs (miRNAs) showed correlation with clinicopathological characteristics. PSA levels were significantly correlated with the Gleason score, tumor stage, and lymph node metastasis with Spearman correlation coefficients: 0.612, 0.576, and 0.458. In conclusion, the combination of the studied circulating plasma miRNAs and serum PSA has the potential to be used as a noninvasive diagnostic biomarker for PC screening outperforming the PSA testing alone.