Urinary hsv2-miR-H9 to hsa-miR-3659 ratio is an effective marker for discriminating prostate cancer from benign prostate hyperplasia in patients within the prostate-specific antigen grey zone

Abstract

Purpose Tumor microRNAs (miRNAs) are released to biofluids directly or indirectly. Although urinary miRNAs are promising non-invasive biomarkers for the diagnosis of prostate cancer (PCa), their clinical application is challenging for technical reasons. We examined the efficacy of urinary hsv2-miR-H9 to hsa-miR-3659 ratio as a non-invasive diagnostic biomarker of PCa. Materials and Methods The expression of urinary miRNAs was quantified by real-time PCR in 116 samples from 53 patients with benign prostatic hyperplasia (BPH) and 63 patients with PCa. The miRNA expression ratio was calculated using an upregulated miRNA (hsv2-miR-H9) as the numerator and a downregulated miRNA (hsa-miR-3659) as the denominator. Results The urinary miR-H9 to miR-3659 ratio was significantly higher in PCa than in BPH controls (p<0.001). The diagnostic accuracy of the urinary miRNA expression ratio was comparable with that of prostate-specific antigen (PSA) (receiver operating characteristic [ROC] curve comparison, p=0.287). The area under the curve for urinary miRNA expression ratio was 0.862 and that for PSA was 0.642 in the “PSA gray zone” (3–10 ng/mL) (ROC curve comparison, p=0.034). The use of the urinary miRNA expression ratio would have prevented 70.6% of unnecessary prostate biopsies; however, 28.6% of PCa cases could be missed in patients within the PSA gray zone. Conclusions The expression ratio of urinary miR-H9 to miR-3659 could be a relevant non-invasive biomarker for PCa diagnosis, particularly for patients within the PSA gray zone.

Urinary MicroRNAs as Biomarkers of Urological Cancers: A Systematic Review

“…In addition, in Kang and colleagues’ study, the expression ratio of urinary miR-H9 to miR-3659 was quantified, and they affirmed that the ratio was significantly higher in the PCa group than in the healthy men group (AUC = 0.803, 95% CI) ( p < 0.001), and that it could represent a non-invasive biomarker for PCa [ 31 ].…”

Retrospective, Evaluator-Blinded, Pilot and Pivotal Clinical Trials: Assessing the mirCaP Kit (hsv2-miR-H9/has-miR-3659) as a Diagnostic Marker for Prostate Cancer in Patients with PSA Gray Zone Levels

“…In a previous study, we determined that the urinary hsv2-miR-H9 to has-miR-3659 expression ratio was a reliable non-invasive diagnostic marker for PCa. 10 In this study, we evaluated the diagnostic and cut-off values of the 'miRCaP' kit (hsv2-miR-H9/has-miR-3659) in the initial clinical trial, and validated its performance as a non-invasive diagnostic marker in a pivotal clinical trial, particularly for patients within the PSA gray zone.…”

“…For example, in the study by Byun et al 11 , approximately 40 positive and 40 negative specimens were collected. Likewise, Kang et al 10 gathered approximately 60 specimens of both positive and negative samples. Informed by these precedents, we chose to collect 140 specimens for our initial clinical trial, consisting of 70 positive and 70 negative specimens, thereby exceeding the sample sizes reported in the referenced literature.…”

“…Recent studies suggest that hsv2-miR-H9 and has-miR-3659 could serve as potential diagnostic markers for PCa. [8][9][10] In this study, we conducted a single center, retrospective, evaluator-blinded, pilot and pivotal clinical trial to assess the clinical performance of the mirCaP kit (hsv2-miR-H9/has-miR-3659) to assist physicians in decision-making for PCa inspections in patients with the PSA gray zone.…”

Exploration of diagnostic biomarkers, microenvironment characteristics, and ursolic acid's therapeutic effect for benign prostate hyperplasia

“…The hsa-miR-221-5p and hsa-miR-708-3p were experimentally verified to be down-regulated in prostate cancer compared to BPH. In particular, the expression ratio of urinary miR-H9 to miR-3659 can be applied for discriminating prostate cancer from BPH, particularly for patients with PSA level in gray zone 24 . The third is the functional protein.…”