A sensitive and specific non-invasive urine biomarker panel for prostate cancer detection.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-01 Epub Date: 2025-09-02 DOI:10.1016/j.ebiom.2025.105895

Menglang Yuan, Marcio Covas Moschovas, Kandarp Joshi, Yohei Sanada, Roshane A Perera, Bongyong Lee, Rudramani Pokhrel, Jiri Polivka, Alexandra Miller, Ernest K Amankwah, Ignacio Gonzalez-Gomez, Naren Nimmagadda, Ezra Baraban, Anant Jaiswal, Cuncong Zhong, Inoel Rivera, Guru P Sonpavde, Chetan Bettegowda, Vipul Patel, Christian P Pavlovich, Ranjan J Perera

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引用次数: 0

Abstract

Background: Prostate cancer (PCa) is one of the leading causes of cancer death in men. While prostate-specific antigen (PSA) testing is widely used for screening, its diagnostic accuracy is limited, often failing to distinguish between benign and malignant prostate conditions, underscoring the need for novel biomarkers with improved diagnostic performance. This study aimed to identify and validate a panel of urinary RNA biomarkers with improved diagnostic accuracy for PCa.

Methods: RNA-sequencing analysis of exfoliated cells in urine specimens identified 50 candidate RNAs. After initial qPCR testing in pooled urine, three biomarkers (TTC3, H4C5, EPCAM) with optimal specificity and sensitivity were selected as a biomarker panel. Diagnostic performance was evaluated in a case-control study divided into development (n = 243 participants) and validation (n = 646 participants) datasets. Biomarker expression was confirmed in tissue specimens, and the oncogenic function of TTC3 was assessed in vitro and in vivo.

Findings: The three-biomarker urine panel robustly identified PCa with an area under the curve (AUC) of 0.96 (95% CI: 0.94-0.98) compared to 0.83 (95% CI: 0.77-0.88) for urinary prostate cancer antigen 3 (PCA3) RNA in the development dataset and 0.92 (95% CI: 0.89-0.94) compared to 0.76 (95% CI: 0.72-0.80) for PCA3 in the validation dataset. Urine biomarkers were nearly eliminated post-prostatectomy and were confirmed to originate from prostate tissue at both the RNA and protein levels. The panel maintained high diagnostic accuracy of PSA-negative PCa cases and distinguished PCa from benign prostate conditions (BPH, prostatitis). Functional studies demonstrated that TTC3 depletion significantly suppressed in vitro and in vivo tumour growth.

Interpretation: This urine-based biomarker panel offers a promising sensitive and specific noninvasive diagnostic for PCa with the potential to form the basis for laboratory-developed and in vitro diagnostic assays.

Funding: This study was supported by the International Prostate Cancer Foundation, JHU SKCCC (grant number P30CA006973), and Bankhead-Coley Cancer Research Program (grant number 24B16) to R. J. Perera and by the Maryland Innovation Initiative Grant to C. P. Pavlovich and R. J. Perera.

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用于前列腺癌检测的一种灵敏、特异的无创尿液生物标志物检测试剂盒。

背景：前列腺癌（PCa）是男性癌症死亡的主要原因之一。虽然前列腺特异性抗原（PSA）检测被广泛用于筛查，但其诊断准确性有限，通常无法区分良性和恶性前列腺疾病，这强调了对具有改进诊断性能的新型生物标志物的需求。本研究旨在鉴定和验证一组尿液RNA生物标志物，以提高前列腺癌的诊断准确性。方法：对尿标本中脱落细胞进行rna测序分析，鉴定出50种候选rna。在汇集的尿液中进行初始qPCR检测后，选择特异性和灵敏度最佳的三个生物标志物（TTC3, H4C5， EPCAM）作为生物标志物面板。诊断性能在病例对照研究中进行评估，该研究分为开发（n = 243名参与者）和验证（n = 646名参与者）数据集。在组织标本中证实了生物标志物的表达，并在体外和体内评估了TTC3的致癌功能。结果：三生物标志物尿液面板强有力地识别出PCa，曲线下面积（AUC）为0.96 (95% CI: 0.94-0.98)，而开发数据集中前列腺癌抗原3 (PCA3) RNA为0.83 (95% CI: 0.77-0.88)，验证数据集中PCA3为0.92 (95% CI: 0.89-0.94)，而PCA3为0.76 （95% CI: 0.72-0.80）。前列腺切除术后尿液生物标志物几乎被消除，并被证实在RNA和蛋白质水平上起源于前列腺组织。该小组对psa阴性的前列腺癌病例保持了较高的诊断准确性，并将前列腺癌与良性前列腺疾病（BPH，前列腺炎）区分开来。功能研究表明，TTC3缺失显著抑制体外和体内肿瘤生长。解释：这种基于尿液的生物标志物面板为前列腺癌提供了一种有希望的敏感和特异性的无创诊断方法，有可能成为实验室开发和体外诊断分析的基础。本研究由国际前列腺癌基金会、JHU SKCCC（资助号P30CA006973）和Bankhead-Coley癌症研究计划（资助号24B16）资助R. J. Perera，并由马里兰州创新倡议资助C. P. Pavlovich和R. J. Perera。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.