title: Different levels of serum microRNAs in prostate cancer and benign prostatic hyperplasia: evaluation of potential diagnostic and prognostic role.
abstract: BACKGROUND
  Diagnosis of prostate cancer (PCa) is based on prostate biopsy that is performed when prostate specific antigen (PSA) is persistently altered over time and/or abnormal digital rectal examination is found. Serum PSA levels increase in both PCa and benign prostatic hyperplasia, leading to an increased number of unnecessary biopsies. There is an urgent need to unravel PCa-specific molecular signatures.
  
  
  METHODS
  This study aimed at characterizing a panel of circulating micro RNAs (miRNAs) that could distinguish PCa from benign prostatic hyperplasia in a population of age-matched patients with increased PSA levels. Both miRNAs targeting genes involved in PCa onset and miRNAs whose role in PCa has been highlighted in other studies were included. For this purpose, let-7c, let-7e, let-7i, miR-26a-5p, miR-26b-5p, miR-24-3p, miR-23b-3p, miR-27-b-3p, miR-106a-5p, miR-20b-5p, miR-18b-5p, miR-19b-2-5p, miR-363-3p, miR-497, miR-195, miR-25-3p, miR-30c-5p, miR-622, miR-874-3p, miR-346 and miR-940 were assayed through real-time PCR in 64 patients with PCa and compared with 60 patients with benign prostatic hyperplasia. The ability of miRNAs to predict the stage of disease was also analyzed.
  
  
  RESULTS
  Let-7c, let-7e, let-7i, miR-26a-5p, miR-26b-5p, miR-18b-5p and miR-25-3p were able to discriminate patients with PCa from those harboring benign prostatic hyperplasia, both presenting altered PSA levels (>3 ng/mL). MiR-25-3p and miR-18b-5p showed the highest sensitivity and specificity to predict PCa, respectively. The combination of these two miRNAs improved the overall sensitivity. A correlation between pathological Gleason score and miRNA expression levels was reported; miR-363-3p, miR-26a-5p, miR-26b-5p, miR-106a-5p, miR-18b-5p, miR-25-3p and let-7i decreased in expression concomitantly with an increase in malignancy.
  
  
  CONCLUSIONS
  This study confirms serum miRNAs to be reliable candidates for the development of minimally invasive biomarkers for the diagnosis and prognosis of PCa, particularly in those cases where PSA acts as a flawed marker.
authors.affiliation: Department of Surgical and Biomedical Sciences, Institution of Urological, Andrological Surgery and Minimally Invasive Techniques.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cochetti
authors.affiliation: Department of Experimental Medicine, Section of Terni.
authors.forename: Giulia
authors.initials: G
authors.lastname: Poli
authors.affiliation: Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Guelfi
authors.affiliation: Department of Surgical and Biomedical Sciences, Institution of Urological, Andrological Surgery and Minimally Invasive Techniques.
authors.forename: Andrea
authors.initials: A
authors.lastname: Boni
authors.affiliation: Department of Surgical and Biomedical Sciences, Institution of Urological, Andrological Surgery and Minimally Invasive Techniques.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Egidi
authors.affiliation: Department of Surgical and Biomedical Sciences, Institution of Urological, Andrological Surgery and Minimally Invasive Techniques.
authors.forename: Ettore
authors.initials: E
authors.lastname: Mearini
keywords: PSA; benign prostatic hyperplasia; miRNA; prostate cancer; serum