Elevated Serum MicroRNA Levels Associate with Absence of High-Grade Prostate Cancer in a Retrospective Cohort

Abstract

To reduce treatment of indolent prostate cancer (PCa), biomarkers are needed to improve identification of patients with a low-risk of having aggressive disease. Over-treatment of these patients occurs because of uncertainty in the aggressiveness of the entire tumor based on the biopsies, which do not accurately sample multifocal tumors. Circulating microRNAs (miRNAs) are stable serum markers and differential miRNA levels occur in men with PCa. The goal of this study was to identify circulating miRNAs that were associated with aggressive or indolent PCa. We measured circulating miRNAs in 150 patients prior to surgery and compared the miRNA levels to the pathology of the entire radical prostatectomy specimen. For this study we used an exceptionally well-characterized cohort of patients who had benign prostatic hyperplasia (BPH), low-grade or high-grade PCa. Low-grade was defined as patients with 100% Gleason grade 3 tumor as determined by step-wise sectioning. High-grade PCa patients had 30-90% Gleason grade 4+5 in the tumor. BPH patients had at least two biopsies negative for PCa. Twenty one miRNAs were selected for analysis. The miRNAs were quantified by RT-qPCR and analyzed by logistic regression. High levels of 14 miRNAs were exclusively present in the serum from patients with low-grade PCa or BPH, compared to men with high-grade PCa who had consistently low levels. The expression levels of the 14 miRNAs were combined into a “miR Score” which had a negative predictive value (NPV) of 0.939 to predict absence of high-grade PCa among PCa and BPH patients. Biochemical recurrence (BCR) was known for the PCa patients and a combined “miR Risk Score” accurately classified a subset of patients with low risk of BCR (NPV 0.941). In summary, measurement of serum miRNAs may have pre-surgical utility in combination with clinical risk calculators to identify patients with low risk of harboring aggressive PCa.

Development of a deregulating MicroRNA panel for the detection of early relapse in postoperative colorectal cancer patients

“…e The samples from early relapse patients showed significantly decreased miR-494 expression levels (P = 0.016). f The samples from early relapsed patients showed significantly decreased let-7b expression levels (P = 0.002) Yang et al J Transl Med (2016) 14:108 that miR-141 has oncogenic characteristics in CRC and prostate cancer [42,43]. Yin et al identified miR-141 as a potential circulating biomarker for metastasis [44], consistent with our findings of high miR-141 expression in early relapsed CRC patients.…”

miRNAs as novel biomarkers in the management of prostate cancer

“…However, the panels proposed for these groups do not overlap in miRNAs composition. On the other hand, downregulated results reported by Mihelich et al [95] concerning miR-93, miR-106a, miR-107, miR-130b and miR-451 were discordant with those reported in the studies made by Moltzahn et al [91], Li et al [97] and Bryant et al [98], which indicated that these miRNAs were upregulated in PCa patients.…”

“…At the moment, the widest study about the clinical usefulness of circulating miRNAs has been performed by Mihelich et al [95], measuring the levels of 21 miRNAs in 50 BPH patients and 100 PCa patients in stages T1-T2, classified according to the Gleason score. The authors proposed a miRNA signature (let7a, miR-103, miR-451, miR-24, miR-26b, miR-30c, miR-93, miR-106a, miR-223, miR-874, miR-146a, miR-125b, miR-100, miR-107 and miR-130b) to predict with high accuracy the absence of high-grade PCa among the BPH and low-grade PCa patients.…”

The translational potential of microRNAs as biofluid markers of urological tumours

“…88 (Table 3) report more promising diagnostic and prognostic data than earlier studies. One reason for this improvement could be that combinations of different miRNAs 111,121 , miRNAs in combination with other markers 113,120 and miRNAs in blood cells 123 or exosomes 124 were investigated, rather than single miRNAs. However, the promising results of these studies are yet to be validated.…”