To improve the selection of patients for ureteroscopy, avoid excessive testing and reduce costs, we aimed to develop and validate a diagnostic urine assay for upper tract urinary carcinoma (UTUC).
In this cohort study we recruited 402 patients from six Hunan hospitals who underwent ureteroscopy for hematuria, including 95 patients with UTUC and 307 patients with non-UTUC findings. Midstream morning urine samples were collected before ureteroscopy and surgery. DNA was extracted and qPCR was used to analyze mutations in TERT and FGFR3 and the methylation of NRN1. In the training set, the random forest algorithm was used to build an optimal panel. Lastly, the Beijing cohort (n = 76) was used to validate the panel.
The panel combining the methylation with mutation markers led to an AUC of 0.958 (95% CI: 0.933-0.975) with a sensitivity of 91.58% and a specificity of 94.79%. The panel presented a favorable diagnostic value for UTUC vs. other malignant tumors (AUC = 0.920) and UTUC vs. benign disease (AUC = 0.975). Furthermore, combining the panel with age revealed satisfactory results, with 93.68% sensitivity, 94.44% specificity, AUC = 0.970 and NPV = 98.6%. In the external validation process, the model showed an AUC of 0.971, a sensitivity of 95.83% and a specificity of 92.31, respectively.
A novel diagnostic model for analyzing hematuria patients for the risk of UTUC was developed, which could lead to a reduction in the need for invasive examinations. Combining NRN1 methylation and gene mutation (FGFR3 and TERT) with age resulted in a validated accurate prediction model.
Cancers. 2022 Jul 21*** epublish ***
Wei Ouyang, Lufeng Luo, Junjie Zhang, Ran Xu, Qiang Lu, Zhenzhou Xu, Jianye Liu, Pei Li, Yaqun Zhang, Chuanchi Zhou, Wei Tang, Zhenting Wang, Manman Cao, Genming Xu, Long Wang
Department of Urology, The Third Xiangya Hospital, Central South University, Changsha 410008, China., Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410028, China., Department of Urology, Hunan Provincial People's Hospital, First Affiliated Hospital of Hunan Normal University, Changsha 410002, China., Department of Urology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medical, Central South University, Changsha 410013, China., Yearth Biotechnology Co., Ltd., Changsha 410205, China., Department of Urology, Beijing Hospital, Beijing 100000, China., Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou 570100, China.