Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada.
Dr. Georges-L.-Dumont University Hospital Centre, Moncton, NB E1C 2Z3, Canada.
Int J Mol Sci. 2020 Nov 6;21(21):8330. doi: 10.3390/ijms21218330.
Serum prostate-specific antigen (sPSA) testing has helped to increase early detection of and decrease mortality from prostate cancer. However, since sPSA lacks specificity, an invasive prostate tissue biopsy is required to confirm cancer diagnosis. Using urinary extracellular vesicles (EVs) as a minimally invasive biomarker source, our goal was to develop a biomarker panel able to distinguish prostate cancer from benign conditions with high accuracy. We enrolled 56 patients in our study, 28 negative and 28 positive for cancer based on tissue biopsy results. Using our Vn96 peptide affinity method, we isolated EVs from post-digital rectal exam urines and used quantitative polymerase chain reaction to measure several mRNA and miRNA targets. We identified a panel of seven mRNA biomarkers whose expression ratio discriminated non-cancer from cancer with an area under the curve (AUC) of 0.825, sensitivity of 75% and specificity of 84%. We also identified two miRNAs whose combined score yielded an AUC of 0.744. A model pairing the seven mRNA and two miRNA panels yielded an AUC of 0.843, sensitivity of 79% and specificity of 89%. Addition of EV-derived PCA3 levels and clinical characteristics to the biomarker model further improved test accuracy. An AUC of 0.955, sensitivity of 86% and specificity of 93% were obtained. Hence, Vn96-isolated urinary EVs are a clinically applicable and minimally invasive source of mRNA and miRNA biomarkers with potential to improve on the accuracy of prostate cancer screening and diagnosis.
血清前列腺特异性抗原（sPSA）检测有助于提高前列腺癌的早期检出率和降低死亡率。然而，由于 sPSA 缺乏特异性，因此需要进行前列腺组织活检以确认癌症诊断。我们利用尿液细胞外囊泡（EVs）作为一种微创生物标志物来源，旨在开发一种能够高准确度地区分前列腺癌与良性疾病的生物标志物组合。我们招募了 56 名患者参与研究，其中 28 名患者的组织活检结果为阴性，28 名为阳性。我们使用 Vn96 肽亲和法从直肠指检后的尿液中分离 EVs，并使用定量聚合酶链反应测量了几种 mRNA 和 miRNA 靶标。我们确定了一个由七个 mRNA 生物标志物组成的表达比值，能够以 0.825 的曲线下面积（AUC）、75%的灵敏度和 84%的特异性区分非癌症和癌症。我们还鉴定出两个 miRNA，它们的联合评分得到的 AUC 为 0.744。一个配对七个 mRNA 和两个 miRNA 面板的模型得到的 AUC 为 0.843，灵敏度为 79%，特异性为 89%。将 EV 衍生的 PCA3 水平和临床特征添加到生物标志物模型中，进一步提高了测试准确性。获得了 AUC 为 0.955、灵敏度为 86%和特异性为 93%的结果。因此，Vn96 分离的尿液 EVs 是一种具有临床应用潜力的微创性 mRNA 和 miRNA 生物标志物来源，有可能提高前列腺癌筛查和诊断的准确性。
