Characterization of Kallireins and microRNAs in Urine Sediment for the Discrimination of Prostate Cancer from Benign Prostatic Hyperplasia

Abstract

Objectives: Prostate Cancer (PCa) and Benign Prostatic Hyperplasia (BPH) are frequently coexisting in elderly men. The measurement of serum PSA together with Digital Rectal Examination (DRE) represents the primary diagnostic tool to suspect PCa, whereas definitive diagnosis is achieved by prostate biopsy. The low specificity of PSA and the modest detection rate of biopsy convict the patient to a quite often unnecessary and uncomfortable clinical itinerary. There is a urgent need for new and more accurate methodologies to diagnosize PCa. In the present study, the expression of 4 mRNAs and 2 miRNAs was evaluated in post DRE urine cell pellets from patients suffering PCa and age-matched subjects affected by BPH with elevated PSA levels. We also evaluated the diagnostic accuracy of markers in predicting PCa. Materials and methods: The expression levels of 4 mRNAs (3 kallikreins - KLK3, KLK11, KLK13 and a prostate cancer antigen - PCA3) and 2 microRNAs (miR-9-3p and miR-19a-3p) were assayed by means of real-time PCR in post DRE urine of 79 men undergoing prostate biopsy for PSA levels > 3 ng/mL. The diagnostic power of tested markers was evaluated through logistic regression analysis. Results: PCA3 was undetectable in 22 out of 38 BPH subjects. KLK3 and KLK11 were significantly upregulated in PCa group (p value < 0.001), while miR-9-3p and miR-19a-3p were up-regulated in BPH group (p value <0.001 and < 0.01, respectively). KLK13 was not differentially expressed between groups. MiR-19a-3p and miR- 9-3p reached the highest specificity (64.29%) and sensitivity (81.08%), respectively. The more accurate bivariate logistic model was obtained combining KLK11 with either miR-9-3p and miR-19a-3p. Conclusions: Our findings demonstrated that selected kallikreins and miRNAs proved to be an accurate diagnostic tool for PCa. Urine cells pellets obtained after DRE represent a reliable biological matrix for minimally invasive gene expression assays.