Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Lawson Health Research Institute, London, ON, Canada.
Prostate Cancer Prostatic Dis. 2021 Sep;24(3):802-811. doi: 10.1038/s41391-021-00319-2. Epub 2021 Feb 15.
Extracellular 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.
STEAP1 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).
Evaluation 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.
STEAP1 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.
细胞外囊泡（EVs）是由所有细胞类型从质膜脱落的具有双层脂膜的细胞来源的结构。在生物体液中存在 EV 的证据促使人们投入大量精力来鉴定其 cargo，并确定其作为癌症非侵入性诊断平台的效用。在这项研究中，我们鉴定了健康男性和前列腺癌患者血浆中存在的循环 STEAP1（前列腺六跨膜上皮抗原 1）阳性 EVs，并评估了其诊断和预后意义。
在前列腺癌患者血浆中鉴定出 STEAP1 存在于 EVs 上。使用电子显微镜、Western blot、纳米颗粒跟踪分析和纳米流式细胞术验证 EVs。对 121 名前列腺癌男性和 55 名健康年龄匹配的对照男性的 STEAP1 阳性 EVs 进行了定量分析。还使用已建立的前列腺癌队列数据（TCGA、MSKCC 和 SU2C/PCF Dream Team）评估了 STEAP1 在前列腺癌组织中的作用。
纳米流式细胞术评估 STEAP1 阳性 EVs 发现，与健康男性相比，前列腺癌患者血浆中的 STEAP1 阳性 EVs 显著增加。然而，总 STEAP1 EV 水平与疾病复发或总生存无关联。前列腺癌组织的队列数据也发现 STEAP1 在前列腺癌中升高，但与复发或总生存无显著关联。
已知 STEAP1 在前列腺细胞中富集，具有潜在的临床意义在前列腺癌中。我们的结果鉴定并定量了血浆中的 STEAP1 阳性 EVs，并为基于 STEAP1 EV 的液体活检作为前列腺癌的诊断策略提供了依据。
