Detection of High-grade Bladder Cancer in Urine Samples Using In Situ Hybridization of Long Noncoding RNA UCA1

Abstract

Objective: 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.

Methods: 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.

Results: 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%.

Conclusion: 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.