Abstract 5546: Urine metabolomic biomarkers discovery for bladder cancer diagnostics
Authors: Schwab Andrew J. , Mitchell Matthew W. , Karoly Edward D. , Sarangarajan Rangaprasad 
Published: April 2023

Abstract
Current estimates in the United States for 2022 are about 81,180 new cases of bladder cancer diagnosis with about 17,100 deaths from the disease (American Cancer Society). Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is the most common type of bladder cancer, approximately 70% of newly diagnosed TCC patients have non-muscle invasive bladder cancer (NMIBC) tumors. The gold standards for initial diagnosis and recurrence of TCC, cystoscopy and cytology, are both limited by their inability to visualize certain areas within the bladder or detect low grade tumors. Moreover, these tests are associated with false positive profiles, with potential for abnormal readouts even in individuals with no obvious signs of cancer. High recurrence rate predicates the need for constant monitoring of signs and symptoms associated with bladder disease following initial diagnosis, and non-invasive diagnostic modalities to detect both recurrent and primary early-stage tumors are a critical unmet need. In this study, comprehensive metabolomic profiling from human urine samples was used to identify and validate a panel of metabolites as potential biomarkers of bladder cancer. Urine samples from 439 total subjects (comprised of 66 bladder cancer, 119 history of bladder cancer but no bladder cancer at time of urine sampling, 58 hematuria subjects, 48 renal cell carcinoma, 58 prostate cancer, and 89 healthy subjects) were analyzed using a proprietary global untargeted metabolomic platform. A follow-up study to determine the reproducibility of the initial data set was conducted with 162 urine samples from subjects with bladder cancer that were either recurrent or primary, or with a negative diagnosis for bladder cancer with a previous history of bladder cancer or had hematuria or urinary voiding issues. Utilizing both data sets, eight biochemicals (lactate, gluconate, palmitoyl sphingomyelin, acetylcarnitine, choline phosphate, succinate, and adenosine) were identified as potential urine biomarkers for bladder cancer. In addition, 3-hydroxybutyrate (BHBA), 2-hydroxybutyrate (AHB), and adipate were identified as potential urine biomarkers for urological cancers. In total, 37 biochemicals have now been identified with having the potential to serve as urine bladder cancer biomarkers, and the majority of the biochemicals identified as biomarkers were associated with biochemical pathways previously shown to be perturbed in bladder tumors. The performance characteristics of the identified biochemicals in the detection of bladder cancer will be reported.
Citation Format: Andrew J. Schwab, Matthew W. Mitchell, Edward D. Karoly, Rangaprasad Sarangarajan. Urine metabolomic biomarkers discovery for bladder cancer diagnostics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5546.