Abstract 3098: Urine-based molecular biomarker signatures for bladder cancer

Abstract

Abstract Introduction: By 2020 the estimated incidence of genitourinary (GU) cancers (prostate, bladder, and kidney) will be over 2 million worldwide and responsible for ∼800 000 deaths. Current diagnosis and monitoring methods of GU cancer patients are often invasive and/or lack sensitivity and specificity. The tremendous success in cell-free DNA (cfDNA) blood test provides a strong rationale for using body fluids such as blood and urine as minimally invasive “liquid biopsies” to identify DNA-based molecular biomarkers in urologic malignancies. Urinary cfDNA as a liquid biopsy holds greater potential for a more sensitive alternative to blood biopsies-based tests for clinical use in GU cancers. Urinary biomarker test offers advantages including the potential for more convenient testing, monitoring, and home use. Methods: Analytic validation was conducted using urine cfDNA samples containing different SNPs with different titrations. Urine samples were collected from two different groups, including treatment-naïve patients with pathology-confirmed bladder cancer (BLCA) and healthy donors. Both tumor and germline tissues were collected from the BLCA patients. Results: We report the development, validation, and clinical application of the urine-based next-generation sequencing for integrated genomic cfDNA profiling of bladder cancers, including genomic alterations, tumor mutation burden (TMB) and microsatellite instability (MSI). The analytic sensitivity goes down to 0.5% with 100% analytical specificity. High concordance for mutations between tumor tissue and urinary cfDNA suggests a higher sensitivity alternative for the non-invasive early detection of BLCA. In addition to the NGS-based test, we also developed a Bio-Rad digital PCR assay for orthogonal confirmation of the detected biomarkers such as FGFR3 hotspot mutations. Conclusions: Our work has demonstrated the promise of using urinary cfDNA for detecting genomic alterations at the early stage of BLCA for biomarker detections. Citation Format: Zhixin Zhao, Amy Chang, Binggang Xiang, Feng Xie, Xiaohong Wang, Kemin Zhou, Jianjun Yu, Pan Du, Shidong Jia. Urine-based molecular biomarker signatures for bladder cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3098.