用于无创检测上尿路上皮癌的多重 RNA 尿液检验的大规模前瞻性验证研究

IF 8.3 1区 医学 Q1 ONCOLOGY
European urology oncology Pub Date : 2024-12-01 Epub Date: 2024-03-23 DOI:10.1016/j.euo.2024.03.005
Hao Zhang, Yue Xu, Kai Wang, Chaoyue Zheng, Yanfeng Li, Huijie Gong, Changming Liu, Mingxiong Sheng, Qinghua Xu, Yifeng Sun, Jinying Chen, Xiaodong Zhang, Changwen Zhang, Hongxian Zhang, Wei Wang
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引用次数: 0

摘要

背景:目前诊断和监测上尿路尿路上皮癌(UTUC)的方法往往是侵入性的、昂贵的,而且对早期和低级别肿瘤无效:验证一种基于尿液的无创 RNA 检测方法,以准确诊断 UTUC:2022年10月至2023年8月期间,在五个临床中心前瞻性地收集了61名UTUC患者和99名未患尿路上皮癌的对照者的尿液样本,然后进行了任何侵入性检查(膀胱镜或输尿管镜)或治疗。所有样本均通过尿液 RNA 检测进行分析,该检测由八个基因组成(CA9、CCL18、ERBB2、IGF2、MMP12、PPP1R14D、SGK2 和 SWINGN)。测试结果显示了每位参与者的风险评分,并以此将患者分为低风险组和高风险组:UTUC的诊断主要基于术前放射学检查标准,并由术后病理结果确认。采用递归特征消除和支持向量机算法、χ2和Student t检验:八基因尿液检验能准确检测出UTUC患者和对照组,在单中心检测队列(n = 93)中的曲线下面积(AUC)为0.901,在多中心临床验证队列(n = 66)中的曲线下面积(AUC)为0.926。在合并验证队列中,八基因尿液检验的灵敏度为 90.16%,特异度为 88.89%,总体准确度为 89.38%。值得注意的是,11 名低水平 UTUC 患者的准确率达到了 100%,表现出色。然而,这项研究仅在术前的一个时间点收集了UTUC患者的尿液,并没有在监测人群的UTUC病理过程中进行连续检测:我们的研究结果表明,尿液八基因检测能准确区分UTUC和其他泌尿系统疾病,具有较高的灵敏度和特异性。在临床实践中,它可用于有效识别UTUC患者,从而减少对输尿管镜检查和盲目手术的依赖。我们发现,从多重 RNA 尿液检验得出的风险评分在 UTUC 患者和相应的对照组之间存在显著差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Large-scale Prospective Validation Study of a Multiplex RNA Urine Test for Noninvasive Detection of Upper Tract Urothelial Carcinoma.

Background: Current approaches for diagnosis and monitoring of upper tract urothelial carcinoma (UTUC) are often invasive, costly, and not efficient for early-stage and low-grade tumors.

Objective: To validate a noninvasive urine-based RNA test for accurate UTUC diagnosis.

Design, setting, and participants: Urine samples were prospectively collected from 61 patients with UTUC and 99 controls without urothelial carcinomas, in five clinical centers between October 2022 and August 2023 prior to any invasive test (cystoscope or ureteroscope) or treatment. All samples were analyzed with a urine-based RNA test composed of eight genes (CA9, CCL18, ERBB2, IGF2, MMP12, PPP1R14D, SGK2, and SWINGN). The test results were presented with a risk score for each participant, which was applied to categorize patients into low- or high-risk groups.

Outcome measurements and statistical analysis: The diagnosis of UTUC was based mainly on preoperative radiological examination criteria and confirmed by postoperative pathological results. The recursive feature elimination and support vector machine algorithms, χ2, and Student t test were used.

Results and limitations: The eight-gene urine test accurately detected UTUC patients and controls with an area under the curve (AUC) of 0.901 in a single-center testing cohort (n = 93) and an AUC of 0.926 in a multicenter clinical validation cohort (n = 66). In the merged validation cohort, the eight-gene urine test achieved high sensitivity of 90.16%, specificity of 88.89%, and overall accuracy of 89.38%. Remarkably, excellent performance was achieved in 11 low-grade UTUC patients with accuracy of 100%. However, this study collected the urine of UTUC patients only at a single preoperative time point and did not perform continuous tests during the pathological process of UTUC in the surveillance population.

Conclusions: Our results demonstrated that the eight-gene urine test can differentiate accurately between UTUC and other urological diseases with high sensitivity and specificity. In clinical practice, it may be used for identifying UTUC patients effectively, leading to reduced reliance on ureteroscopy and blind surgery.

Patient summary: In this study, we investigated a multiplex RNA urine test for noninvasive upper tract urothelial carcinoma (UTUC) diagnosis before treatment. We found that the risk scores derived from the multiplex RNA urine test differed significantly between UTUC patients and corresponding controls.

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来源期刊
CiteScore
15.50
自引率
2.40%
发文量
128
审稿时长
20 days
期刊介绍: Journal Name: European Urology Oncology Affiliation: Official Journal of the European Association of Urology Focus: First official publication of the EAU fully devoted to the study of genitourinary malignancies Aims to deliver high-quality research Content: Includes original articles, opinion piece editorials, and invited reviews Covers clinical, basic, and translational research Publication Frequency: Six times a year in electronic format
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