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Supplementary Table S4 from Deep Sequencing of Urinary RNAs for Bladder Cancer Molecular Diagnostics

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posted on 2023-03-31, 20:06 authored by Mandy L.Y. Sin, Kathleen E. Mach, Rahul Sinha, Fan Wu, Dharati R. Trivedi, Emanuela Altobelli, Kristin C. Jensen, Debashis Sahoo, Ying Lu, Joseph C. Liao

Full list of differentially expressed genes identified in comparison of the 10 HG bladder cancer urine samples to 3 LG bladder cancer urine samples based on urinary RNA-seq data in the urinary biomarker discovery.

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ARTICLE ABSTRACT

Purpose: The majority of bladder cancer patients present with localized disease and are managed by transurethral resection. However, the high rate of recurrence necessitates lifetime cystoscopic surveillance. Developing a sensitive and specific urine-based test would significantly improve bladder cancer screening, detection, and surveillance.Experimental Design: RNA-seq was used for biomarker discovery to directly assess the gene expression profile of exfoliated urothelial cells in urine derived from bladder cancer patients (n = 13) and controls (n = 10). Eight bladder cancer specific and 3 reference genes identified by RNA-seq were quantitated by qPCR in a training cohort of 102 urine samples. A diagnostic model based on the training cohort was constructed using multiple logistic regression. The model was further validated in an independent cohort of 101 urines.Results: A total of 418 genes were found to be differentially expressed between bladder cancer and controls. Validation of a subset of these genes was used to construct an equation for computing a probability of bladder cancer score (PBC) based on expression of three markers (ROBO1, WNT5A, and CDC42BPB). Setting PBC = 0.45 as the cutoff for a positive test, urine testing using the three-marker panel had overall 88% sensitivity and 92% specificity in the training cohort. The accuracy of the three-marker panel in the independent validation cohort yielded an AUC of 0.87 and overall 83% sensitivity and 89% specificity.Conclusions: Urine-based molecular diagnostics using this three-marker signature could provide a valuable adjunct to cystoscopy and may lead to a reduction of unnecessary procedures for bladder cancer diagnosis. Clin Cancer Res; 23(14); 3700–10. ©2017 AACR.