A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2-10 ng/mL at initial biopsy

Mol Cancer. 2021 Jul 23;20(1):96. doi: 10.1186/s12943-021-01388-6.

Abstract

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

Keywords: Circular RNA (circRNA); Diagnosis; Extracellular vesicle; Prostate cancer; Urine.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor*
  • Biopsy
  • Cell-Free Nucleic Acids*
  • Extracellular Vesicles / metabolism*
  • Gene Expression Profiling
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Neoplasm Grading
  • Prognosis
  • Prostate-Specific Antigen / urine*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / urine*
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • ROC Curve
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • RNA, Circular
  • Prostate-Specific Antigen