Higgins Michelle I, Li Jiangfeng, Ahmed Waqar, Lu Changxue, Horie Kengo, Cheaib Joseph G, Sepehri Sadra, VandenBussche Christopher J, Luo Jun, Kates Max
Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD; The Greenberg Bladder Cancer Institute at Johns Hopkins, Marburg Building, Johns Hopkins Hospital, Baltimore, MD.
Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Urology. 2025 Jul;201:77-83. doi: 10.1016/j.urology.2025.05.012. Epub 2025 May 13.
To evaluate the performance of urinary biomarker long noncoding RNA urothelial carcinoma-associated 1 (UCA1) in detection of high-grade bladder cancer (BCa) using RNA in situ hybridization (RISH). Urine cytology and cystoscopy are the gold standard for BCa detection. There is a paucity of reliable urinary biomarkers for BCa detection in clinical practice.
TCGA and Cancer Cell Line Encyclopedia databases were utilized to analyze the expression pattern of UCA1 in BCa surgical specimens and cell lines. A method for detection of UCA1 expression on cytology slides was developed. Urine and pathology samples were collected from patients undergoing trans-urethral resection of bladder tumor or radical cystectomy. Performance of RISH and cytology were evaluated for detection of high-grade BCa, vs low-grade and no BCa. The sensitivity, specificity, positive predictive value, negative predictive value (NPV) of RISH alone, cytology alone, and sequential use of cytology followed by RISH in cases of atypical or negative cytology were calculated.
UCA1 was significantly upregulated in BCa tissues compared to normal controls. In 50 patients with a confirmed diagnosis of BCa, urine cytology had a sensitivity 34.4%, NPV 36.4% for detection of high grade BCa. RISH had a sensitivity 66.7%, NPV 50%. Sequential testing including both cytology and RISH revealed a sensitivity 78.1%, NPV 53.3%.
UCA1 improves sensitivity and NPV of urine cytology alone for detection of high grade BCa. This pilot study demonstrates potential utility of UCA1 as a urinary biomarker to augment cytology for screening and surveillance of high grade BCa.
通过RNA原位杂交（RISH）评估尿生物标志物长链非编码RNA尿路上皮癌相关1（UCA1）在检测高级别膀胱癌（BCa）中的性能。尿细胞学检查和膀胱镜检查是BCa检测的金标准。在临床实践中，缺乏用于BCa检测的可靠尿生物标志物。
利用TCGA和癌细胞系百科全书数据库分析UCA1在BCa手术标本和细胞系中的表达模式。开发了一种在细胞学载玻片上检测UCA1表达的方法。从接受经尿道膀胱肿瘤切除术或根治性膀胱切除术的患者中收集尿液和病理样本。评估RISH和细胞学检查在检测高级别BCa与低级别和无BCa方面的性能。计算单独使用RISH、单独使用细胞学检查以及在非典型或阴性细胞学检查病例中先进行细胞学检查后再进行RISH的敏感性、特异性、阳性预测值、阴性预测值（NPV）。
与正常对照相比，UCA1在BCa组织中显著上调。在50例确诊为BCa的患者中，尿细胞学检查检测高级别BCa的敏感性为34.4%，NPV为36.4%。RISH的敏感性为66.7%，NPV为50%。包括细胞学检查和RISH的序贯检测显示敏感性为78.1%，NPV为53.3%。
UCA1提高了单独尿细胞学检查检测高级别BCa的敏感性和NPV。这项初步研究证明了UCA1作为尿生物标志物在增强细胞学检查用于高级别BCa筛查和监测方面的潜在效用。
