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Detection of High-grade Bladder Cancer in Urine Samples Using In Situ Hybridization of Long Noncoding RNA UCA1
Michelle I Higgins1, Jiangfeng Li2, Waqar Ahmed3
1Department 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.
Urology
|May 15, 2025
Summary
The long noncoding RNA urothelial carcinoma-associated 1 (UCA1) shows promise as a urinary biomarker. UCA1, when used with urine cytology, improves the detection of high-grade bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Bladder cancer (BCa) detection relies on urine cytology and cystoscopy, with a need for improved urinary biomarkers.
- Urothelial carcinoma-associated 1 (UCA1) is a long noncoding RNA investigated for its potential role in BCa.
Purpose of the Study:
- To evaluate the diagnostic performance of the urinary biomarker UCA1 for high-grade bladder cancer (BCa) detection using RNA in situ hybridization (RISH).
Main Methods:
- Analyzed UCA1 expression in BCa tissues and cell lines using TCGA and Cancer Cell Line Encyclopedia databases.
- Developed and validated a RISH method for UCA1 detection on cytology slides.
- Assessed the sensitivity, specificity, and predictive values of RISH, cytology, and sequential testing in 50 BCa patients.
Main Results:
- UCA1 was significantly upregulated in BCa tissues.
- For high-grade BCa, RISH sensitivity was 66.7% and NPV was 50%, compared to 34.4% sensitivity and 36.4% NPV for cytology alone.
- Sequential testing with cytology and RISH achieved 78.1% sensitivity and 53.3% NPV.
Conclusions:
- UCA1 significantly enhances the sensitivity and negative predictive value of urine cytology for detecting high-grade BCa.
- This pilot study suggests UCA1 is a valuable urinary biomarker for augmenting cytology in screening and surveillance of high-grade BCa.

