Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes

Nat Commun. 2020 Apr 24;11(1):1987. doi: 10.1038/s41467-020-15913-6.


Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is among the most common diseases affecting aging men, but the underlying molecular features remain poorly understood, and therapeutic options are limited. Here we employ a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling. We find no evidence of neoplastic features in BPH: no evidence of driver genomic alterations, including low coding mutation rates, mutational signatures consistent with aging tissues, minimal copy number alterations, and no genomic rearrangements. At the epigenetic level, global hypermethylation is the dominant process. Integrating transcriptional and methylation signatures identifies two BPH subgroups with distinct clinical features and signaling pathways, validated in two independent cohorts. Finally, mTOR inhibitors emerge as a potential subtype-specific therapeutic option, and men exposed to mTOR inhibitors show a significant decrease in prostate size. We conclude that BPH consists of distinct molecular subgroups, with potential for subtype-specific precision therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Biomarkers / analysis
  • DNA Methylation
  • Epigenesis, Genetic
  • Epigenomics
  • Genomics
  • Humans
  • Male
  • Middle Aged
  • Mutation Rate
  • Organ Size / drug effects
  • Organ Size / genetics
  • Precision Medicine / methods
  • Prospective Studies
  • Prostate / diagnostic imaging
  • Prostate / drug effects
  • Prostate / pathology*
  • Prostatic Hyperplasia / diagnostic imaging
  • Prostatic Hyperplasia / drug therapy
  • Prostatic Hyperplasia / genetics*
  • Prostatic Hyperplasia / pathology
  • RNA-Seq
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Sirolimus / analogs & derivatives
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Urological Agents / pharmacology
  • Urological Agents / therapeutic use*
  • Whole Genome Sequencing


  • Biomarkers
  • Urological Agents
  • temsirolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus