Clinical significance of STEAP1 extracellular vesicles in prostate cancer

Karan Khanna,Hon S Leong,Karla C Williams,Kalan S Lynn,Nikki Salmond

doi:10.1038/s41391-021-00319-2

Abstract

BackgroundExtracellular vesicles (EVs) are cell-derived lipid bilayer enclosed structures shed from the plasma membrane by all cell types. Evidence of EV presence in biological fluids has led to considerable efforts focused on identifying their cargo and determining their utility as a non-invasive diagnostic platform for cancer. In this study, we identify circulating STEAP1 (six-transmembrane epithelial antigen of the prostate 1)-positive EVs in the plasma of healthy males and prostate cancer patients and evaluate its diagnostic and prognostic significance.MethodsSTEAP1 was identified on EVs in prostate cancer patient plasma. EVs were validated using electron microscopy, Western blot, nanoparticle tracking analysis, and nanoscale flow cytometry. STEAP1-positive EVs were quantified for 121 males with prostate cancer and 55 healthy age-matched control males. An evaluation of STEAP1 in prostate cancer tissue was also performed using established prostate cancer cohort data (TCGA, MSKCC, and SU2C/PCF Dream Team).ResultsEvaluation of STEAP1-positive EVs by nanoscale flow cytometry identified a significant increase in prostate cancer patient plasma compared to healthy males. However, no association was found between total STEAP1 EV levels and disease recurrence or overall survival. Cohort data from prostate cancer tissue also found STEAP1 to be elevated in prostate cancer while no significant association with recurrence or overall survival was identified.ConclusionsSTEAP1 is known to be enriched on the cells of the prostate with potential clinical significance in prostate cancer. Our results identify and quantitate STEAP1-positive EVs in plasma and provide rationale for a STEAP1 EV-based liquid biopsy as a diagnostic strategy in prostate cancer.

Highlights

IntroductionScreening for Prostate cancer (PCa) using the prostate-specific antigen test (PSA) has reduced the incidence of late-stage PCa and PCa mortality [1]
To determine if STEAP1 could be detected on circulating Extracellular vesicles (EVs) in the blood, EVs were isolated from the plasma of individuals with a biopsy confirmed diagnosis of Prostate cancer (PCa) and assessed for STEAP1 expression (Fig. 1)
size-exclusion chromatography (SEC) was used to isolate EVs from the plasma of PCa patients and isolated factions were analysed for EVs using scanning transmission electron microscope (STEM), Western blot, and nanoparticle tracking analysis (Fig. 1A–E)

Summary

Introduction

Screening for PCa using the prostate-specific antigen test (PSA) has reduced the incidence of late-stage PCa and PCa mortality [1] It is associated with an increase in the detection of benign and non-cancerous lesions [1, 2]. We identify circulating STEAP1 (six-transmembrane epithelial antigen of the prostate 1)-positive EVs in the plasma of healthy males and prostate cancer patients and evaluate its diagnostic and prognostic significance. Results Evaluation of STEAP1-positive EVs by nanoscale flow cytometry identified a significant increase in prostate cancer patient plasma compared to healthy males. Cohort data from prostate cancer tissue found STEAP1 to be elevated in prostate cancer while no significant association with recurrence or overall survival was identified. Our results identify and quantitate STEAP1-positive EVs in plasma and provide rationale for a STEAP1 EV-based liquid biopsy as a diagnostic strategy in prostate cancer

Methods

Results

Conclusion