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. 2021 Apr 25;13(9):2068.
doi: 10.3390/cancers13092068.

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

Irena Abramovic  1   2   3 , Borna Vrhovec  4 , Lucija Skara  1   2   3 , Alen Vrtaric  3   5 , Nora Nikolac Gabaj  3   5   6 , Tomislav Kulis  2   3   7 , Goran Stimac  2   4 , Dejan Ljiljak  8 , Boris Ruzic  2   3   4 , Zeljko Kastelan  2   3   7 , Bozo Kruslin  3   9 , Floriana Bulic-Jakus  1   2   3 , Monika Ulamec  2   3   9   10 , Ana Katusic-Bojanac  1   3 , Nino Sincic  1   2   3
Affiliations

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

Irena Abramovic et al. Cancers (Basel). .

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.

Keywords: benign prostate hyperplasia; biomarkers; liquid biopsy; microRNA; plasma; prostate cancer; seminal fluid.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Blood and seminal plasma miRNA levels in PCa patients compared to BPH patients. Significant differences between groups are indicated: * p < 0.05.
Figure 2
Figure 2
ROC curve analysis of the combinations miR-375-3p/miR-182-5p/PSA and miR-375-3p/miR-182-5p/PSA using sub-cohort of PCa patients with serum PSA levels ≤10 µg/L. is a figure.
Figure 3
Figure 3
Blood and seminal plasma levels of miR-21-5p in PCa patients with WHO 2016/ISUP grade groups 1–2 compared to WHO 2016/ISUP grade groups 3–5. Significant differences between grade groups are indicated: * p < 0.05 and seminal plasma miRNA levels in PCa patients compared to BPH patients. Significant differences between groups are indicated: * p < 0.05.
Figure 4
Figure 4
Seminal plasma expression of miR-375-3p, miR-182-5p, and miR-21-5p in PCa patients with serum PSA levels ≤10 vs >10 µg/L. Significant differences between groups are indicated: * p < 0.05; ** p < 0.01.
See this image and copyright information in PMC

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