Small RNAs as biomarkers to differentiate benign and malign prostate diseases: An alternative for transrectal punch biopsy of the prostate?

PLoS One. 2021 Mar 24;16(3):e0247930. doi: 10.1371/journal.pone.0247930. eCollection 2021.


Prostate cancer (PCa) is the most common cancer and the third most frequent cause of male cancer death in Germany. MicroRNAs (miRNA) appear to be involved in the development and progression of PCa. A diagnostic differentiation from benign prostate hyperplasia (BPH) is often only possible through transrectal punch biopsy. This procedure is described as painful and carries risks. It was investigated whether urinary miRNAs can be used as biomarkers to differentiate the prostate diseases above. Therefore urine samples from urological patients with BPH (25) or PCa (28) were analysed using Next-Generation Sequencing to detect the expression profile of total and exosomal miRNA/piRNA. 79 miRNAs and 5 piwi-interacting RNAs (piRNAs) were significantly differentially expressed (adjusted p-value < 0.05 and log2-Fc > 1 or < -1). Of these, 6 miRNAs and 2 piRNAs could be statistically validated (AUC on test cohort > = 0.7). In addition, machine-learning algorithms were used to identify a panel of 22 additional miRNAs, whose interaction makes it possible to differentiate the groups as well. There are promising individual candidates for potential use as biomarkers in prostate cancer. The innovative approach of applying machine learning methods to this kind of data could lead to further small RNAs coming into scientific focus, which have so far been neglected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Diagnosis, Differential
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Diseases / diagnosis*
  • Prostatic Diseases / genetics
  • Prostatic Diseases / metabolism
  • Prostatic Diseases / pathology
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology


  • Biomarkers
  • Biomarkers, Tumor
  • MicroRNAs

Grant support

LM, JH, AS, CK, MK and AS were funded by the Paul-Kuth-Foundation, Wuppertal, Germany, for this study with 43.175€. (AZ310, The funding institution did not have any influence on the setting, implementation, analysis, evaluation and publication of the study. The work of KS, MT and ME was supported by de.NBI (FKZ 031 A 534A), a project of the German Federal Ministry of Education and Research. The funding of ME relates to PURE and VALIBIO, projects of Northrhine-Westphalia. (