Development of a Technique for Diagnosis and Screening of Superficial Bladder Cancer by Cell-Pellet DNA From Urine Sample

Bladder cancer (BCa) is the most common malignancy of the urinary system with high incidence and recurrence rates. There are several ways to detect BCa. However, different approaches have different accuracy, which essentially depends on the sensitivity and specificity of the technique. Alternative noninvasive diagnostic tools for BCa are needed. We isolated and compared urinary cell-pellet DNA (cpDNA), cell-free DNA, and exosomal DNA from patients with localized BCa. Consequently, we analyzed 12 tissues and cpDNA samples by next-generation sequencing and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and noncoding sequences. Then, cpDNA and tissue DNA from 12 patients were analyzed using next-generation sequencing to verify that the genomic characteristics of cpDNA are concordant with those of tissue. We also detected somatic mutation patterns between tissues and their corresponding cpDNA samples. An overlapping variant analysis was performed based on somatic mutation data and a high similarity was observed. Moreover, we identified frequently mutated signaling pathways. In these results, several point mutations were analyzed in FGFR3, TTN, and LEPROTL1 from the cpDNA of patients with BCa. Tumor mutational burden analysis showed that cpDNA had no significant difference in tumor mutational burden compared with tumor tissue. These results provide that cpDNA is a potential diagnostic source for detecting and managing BCa using alternative noninvasive methods from patient urine. Our findings may serve as a clinical tool for early detection or recurrence screening of nonmuscle invasive BCa using urinary cpDNA.