214P - Development and prospective validation of a multiplex RNA urine test for noninvasive detection and surveillance of urothelial carcinoma

Background

Urothelial carcinoma (UC), including upper tract UC (UTUC) and UC of the bladder (UCB), is one of the most common malignancies worldwide. The current standard methods for diagnosis and monitoring of UC are often invasive and/or lack sensitivity and specificity. Emerging evidence has shown that urinary RNAs could potentially serve as promising biomarkers for UC diagnosis. In this study, we intended to develop and validate an accurate and noninvasive urine RNA test for UC diagnosis and monitoring.

Methods

Gene expression profiling of our previously reported 32 RNA targets were analyzed TaqMan qPCR arrays. We pooled all samples analyzed before to obtain a larger training set and develop a diagnostic gene panel. The identified gene panel was then validated in a large-scale independent cohort of 752 patients. Voided urine specimens were prospectively collected at 3 hospitals from subjects scheduled for tumor surgery or endoscopy for the urinary tract due to suspicious symptoms. The sensitivity and specificity of the gene panel were evaluated using endoscopy and/or histologic diagnosis as a reference.

Results

An eight-gene panel (CA9, CCL18, ERBB2, IGF2, MMP12, PPP1R14D, SGK2 and SWINGN) was developed. In the prospective cohort, the gene panel achieved 93.4%overall accuracy (702/752), 92.3% sensitivity (275/298) and 94.1% specificity (427/454). High sensitivity was maintained in low grade (89.9%, 62/69), early stage (88.5%, 115/130) and residual tumors (89.5%, 34/38). Notably, the gene panel accurately detected UTUCs with 97.3% (36/37) sensitivity, indicating that urinary RNA targets selected here were relevant markers for both UTUC and UCB. Besides, the specificity among other malignancies like prostate cancer, renal cancer, etc. reached 94.5% (173/183). With respect to surveillance, the gene panel showed 88.6% sensitivity and 98.2% specificity for detecting recurrences in 136 patients.

Conclusions

In summary, the eight-gene urine test showed superior sensitivity and specificity for diagnosis of UCs across all tumor stages, grades and sites, hence might represent a promising tool for noninvasive UC detection and surveillance.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Canhelp Genomics.

Disclosure

Y. Wo, Z. Luo, J. Chen, Q. Xu: Financial Interests, Personal, Full or part-time Employment: Canhelp Genomics. All other authors have declared no conflicts of interest.