A model to detect significant prostate cancer integrating urinary peptide and extracellular vesicle RNA data

Shea Connell, Maria Frantzi, Agnieszka Latosinska, Martyn Webb, William Mullen, Martin Pejchinovski, Mark Salji, Harald Mischak, Colin Cooper, Jeremy Clark, Daniel Brewer

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Abstract

There is a clinical need to improve assessment of biopsy-naïve patients for the presence of clinically significant prostate cancer (PCa). In this study, we investigated whether the robust integration of expression data from urinary extracellular vesicle RNA (EV-RNA) with urine proteomic metabolites can accurately predict PCa biopsy outcome. Urine samples collected within the Movember GAP1 Urine Biomarker study (n = 192) were analysed by both mass spectrometry-based urine-proteomics and NanoString gene-expression analysis (167 gene-probes). Cross-validated LASSO penalised regression and Random Forests identified a combination of clinical and urinary biomarkers for predictive modelling of significant disease (Gleason Score (Gs) ≥ 3 + 4). Four predictive models were developed: ‘MassSpec’ (CE-MS proteomics), ‘EV-RNA’, and ‘SoC’ (standard of care) clinical data models, alongside a fully integrated omics-model, deemed ‘ExoSpec’. ExoSpec (incorporating four gene transcripts, six peptides, and two clinical variables) is the best model for predicting Gs ≥ 3 + 4 at initial biopsy (AUC = 0.83, 95% CI: 0.77–0.88) and is superior to a standard of care (SoC) model utilising clinical data alone (AUC = 0.71, p < 0.001, 1000 resamples). As the ExoSpec Risk Score increases, the likelihood of higher-grade PCa on biopsy is significantly greater (OR = 2.8, 95% CI: 2.1–3.7). The decision curve analyses reveals that ExoSpec provides a net benefit over SoC and could reduce unnecessary biopsies by 30%.

Original languageEnglish
Article number1995
JournalCancers
Volume14
Issue number8
DOIs
Publication statusPublished - 14 Apr 2022

Keywords

  • extraceullar vesicles
  • Mass Spectrometry
  • prostate cancer
  • urinary biomarkers
  • RNA
  • extracellular vesicles
  • mass spectrometry

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