Candidate Urine microRNA Biomarkers Differentially Expressed in Preoperative Urine Specimens from Patients With pT0 Compared to Muscle Invasive Urothelial Carcinoma at Time of Cystectomy
Amanda Sherman, MD, Travis Sullivan, MS, Kimberly Rieger-Christ, PhD.
Lahey Hospital and Medical Center, Burlington, MA, USA.
Background: Radical cystectomy with urinary diversion is crucial in managing muscle invasive bladder cancer (MIBC). Despite the increasing adoption of minimally invasive techniques to perform the operation, it remains a morbid procedure with a relatively high rate of accepted post-operative complications. A small, but significant number of patients undergoing the procedure have T0 disease on pathologic examination. This study aims to identify these pT0 patients using microRNA (miRNA) profiles from preoperative urine specimens.
Methods:Total RNA was isolated from cell-free urine of patients undergoing cystectomy for a history of muscle-invasive cancer. Each sample was profiled for 376 unique miRNA using a novel qPCR based detection system (MIRXES). Statistical evaluations were performed to determine the potential of miRNA to distinguish these cohorts using receiver operator characteristic curves.
Results: Urine samples from twenty four patients were analyzed: twelve from patients with subsequently confirmed muscle invasive bladder cancer and twelve patients with pathology of pT0. Clinical characteristics were similar between the groups. 144 miRNA were detected in each of the samples from pT0 patients while 215 were detected in each of the samples from the muscle invasive cohort. Nine miRNA were significantly differentially expressed between the cohorts (P<0.05). Seven of these achieved an AUC>0.75 for distinguishing MIBC.
Conclusions: This novel qPCR analysis of preoperative urine specimens was successful in identifying candidate miRNA to be further evaluated as a noninvasive test to detect eradication of MIBC prior to cystectomy. Of 9 total miRNAs that are differentially expressed in urine between pT0 and MIBC specimens, 7 exhibit an AUC> 0.75, strengthening their candidacy as markers. Validation with further samples is planned, and once complete, inquiry will shift towards optimizing a urine assay for use in clinical surveillance, intended to detect patients in whom cystectomy can be safely delayed or deferred. Subgroup analysis comparing differential expression based on type of neoadjuvant treatment is another planned direction for expansion of investigation. 
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