Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential.

Jacob Fredsøe,Michael Borre,Marianne T Bjerre,Karina D Sørensen,Peter Mouritzen,Anne K I Rasmussen,Mikkel Fode,Peter Østergren

doi:10.3390/diagnostics10040188

Jacob Fredsøe, Michael Borre + Show 6 more

Open Access

https://doi.org/10.3390/diagnostics10040188

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Abstract

Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAs in plasma, we confirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375*miR-33a-5p/miR-16-5p*miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

Highlights

With more than one million cases diagnosed annually, prostate cancer (PC) is one of the most common cancer types in males in the Western world [1]
In order to investigate the potential of miRNA in plasma as diagnostic biomarker candidates for PC, we analyzed the expression levels of 92 unique miRNAs in plasma samples from 144 patients with benign prostatic hyperplasia (BPH), 407 patients with clinically localized prostate cancer (LPC), and 57 patients with hormone naïve advanced prostate cancer (APC) (Table 1)
We identified multiple significantly dysregulated miRNAs between the groups, but few miRNAs were significantly associated with PC

Summary

Introduction

With more than one million cases diagnosed annually, prostate cancer (PC) is one of the most common cancer types in males in the Western world [1]. Is generally curable by surgery or radiation therapy with a 5-year survival rate of close to 100% while metastatic prostate cancer (MPC) is generally incurable and has a 5-year survival rate below 40% [2,3]. The primary diagnosis of PC is typically performed by transrectal ultrasound guided biopsies (TRUSbx) of the prostate, prompted by increased serum levels of prostate specific antigen (PSA). /or suspicious findings on digital rectal examination (DRE). This approach is suboptimal, resulting in up to 75% of all initial TRUS-biopsies being negative [4], while still missing 25% of clinically significant cancers [5]. Multiparametric MRI (mpMRI) with MRI-targeted biopsies has been proven to be an improvement for PC detection over standard systematic TRUSbx [8,9,10]

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