The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

中文翻译：

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一种尿液细胞外囊泡 circRNA 分类器，用于检测初始活检时前列腺特异性抗原为 2-10 ng/mL 的患者的高级别前列腺癌

本研究的目的是确定一种尿液细胞外囊泡环状 RNA (circRNA) 分类器，该分类器可以检测 GG 2 级或更高级别的高级别前列腺癌 (PCa)。为此，我们使用 RNA 测序从 11 名高级别 PCa 患者和 11 名良性前列腺增生患者的尿细胞外囊泡中鉴定候选 circRNA。在训练队列（n = 263）中使用 ddPCR，我们构建了一个尿液细胞外囊泡 circRNA 分类器（Ccirc，包含 circPDLIM5、circSCAF8、circPLXDC2、circSCAMP1 和 circCCNT2），并在两个独立队列（n = 497，n = 505)。在训练队列和验证队列中，Ccirc 显示出比两个标准护理风险计算器 (RC)（PCPT-RC 2.0 和 ERSPC-RC）更高的准确性。在所有三个队列中，这种新型尿液细胞外囊泡 circRNA 分类器加 RC 在预测 ≥ GG2 PCa 方面比单独的 RC 在统计学上更具预测性。这种检测不需要预采集直肠指检或特殊处理，是可重复的、无创的，并且可以作为基本临床工作流程的一部分轻松实施。