Urine Based Liquid Biopsy Assist Evaluating Upper Tract Urinary Carcinoma Risk of Patients with Hematuria

Background: In the large amount of hematuria patients, a considerable part of them originate in upper tract urinary carcinoma(UTUC). The most important in the evaluation of hematuria is to find accurate and economical method to discriminate between non-malignant and malignant causes. Liquid biopsy for urine samples can be helpful for UTUC diagnosis in patients with hematuria and rule out individuals with low-risk. Methods: In this study, we combined high-throughput sequencing of 17 genes and methylation analysis for ONECUT2 CpG sites as a liquid biopsy panel. We developed a prediction model which contained several significant features to evaluate the risk of UTUC in hematuria patients. Findings: 94 healthy, 70 UTUC- and 70 UTUC+ cases’ samples are qualified for this study, our liquid biopsy panel resulting in a sensitivity of 94% (66/70), and a specificity of 96% (158/164), the positive predication value of 92% and a negative predication value of 98% in this study. With age as additional factor, our model was able to stratify patients into a low or high-risk group with an accuracy score at 94%. Further validation in a large prospective cohort will answer whether this early screening tool can also be used in monitoring postoperative patients who need serials of follow-ups. Interpretation: Urine based liquid biopsy can assist evaluating upper tract urinary carcinoma risk of patients with hematuria and outperformed FISH for accurately ruling out patients who do not have UTUC. Funding Statement: In this research, no funding or other financial supports was received. Declaration of Interests: The authors declared that they have no conflicts of interest to this study. Ethics Approval Statement: Informed written consent was obtained from patients at PLA General Hospital and the study was approved by the Committees on Clinical Research Ethics of the Chinese PLA General Hospital.