Transcript Markers from Urinary Extracellular Vesicles for Predicting Risk Reclassification of Prostate Cancer Patients on Active Surveillance

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Serum prostate-specific antigen (PSA), its derivatives, and magnetic resonance tomography (MRI) lack sufficient specificity and sensitivity for the prediction of risk reclassification of prostate cancer (PCa) patients on active surveillance (AS). We investigated selected transcripts in urinary extracellular vesicles (uEV) from PCa patients on AS to predict PCa risk reclassification (defined by ISUP 1 with PSA > 10 ng/mL or ISUP 2-5 with any PSA level) in control biopsy. Before the control biopsy, urine samples were prospectively collected from 72 patients, of whom 43% were reclassified during AS. Following RNA isolation from uEV, multiplexed reverse transcription, and pre-amplification, 29 PCa-associated transcripts were quantified by quantitative PCR. The predictive ability of the transcripts to indicate PCa risk reclassification was assessed by receiver operating characteristic (ROC) curve analyses via calculation of the area under the curve (AUC) and was then compared to clinical parameters followed by multivariate regression analysis. ROC curve analyses revealed a predictive potential for AMACR, HPN, MALAT1, PCA3, and PCAT29 (AUC = 0.614-0.655, p < 0.1). PSA, PSA density, PSA velocity, and MRI maxPI-RADS showed AUC values of 0.681-0.747 ( p < 0.05), with accuracies for indicating a PCa risk reclassification of 64-68%. A model including AMACR, MALAT1, PCAT29, PSA density, and MRI maxPI-RADS resulted in an AUC of 0.867 ( p < 0.001) with a sensitivity, specificity, and accuracy of 87%, 83%, and 85%, respectively, thus surpassing the predictive power of the individual markers. These findings highlight the potential of uEV transcripts in combination with clinical parameters as monitoring markers during the AS of PCa.

Details

Original languageEnglish
Article number2453
JournalCancers
Volume16
Issue number13
Publication statusPublished - 4 Jul 2024
Peer-reviewedYes

External IDs

PubMedCentral PMC11240337
ORCID /0000-0003-3717-3637/work/164195940
Scopus 85198400077

Keywords

Sustainable Development Goals

Keywords

  • active surveillance, biomarker, liquid biopsy, monitoring, prediction, prostate cancer, quantitative PCR, risk reclassification, transcripts, urinary extracellular vesicles