阶段(地层学)
肿瘤科
医学
尿路上皮癌
接收机工作特性
膀胱癌
生物标志物
甲基化
队列
内科学
尿
DNA甲基化
切断
曲线下面积
癌变
生物
癌症
遗传学
DNA
基因
古生物学
基因表达
物理
量子力学
作者
Junjie Zhang,Ran Xu,Qiang Lü,Zhongzhi Xu,Jianye Liu,Pei Li,Yaqun Zhang,Chuanchi Zhou,Lufeng Luo,Wei Tang,Zhenting Wang,Manman Cao,Jian Cao,Genming Xu,Long Wang
出处
期刊:Cancers
[MDPI AG]
日期:2023-01-19
卷期号:15 (3): 615-615
被引量:2
标识
DOI:10.3390/cancers15030615
摘要
Aberrant DNA methylation is an early event during tumorigenesis. In the present study, we aimed to construct a methylation diagnostic tool using urine sediment for the detection of urothelial bladder carcinoma, and improved the diagnostic performance of the model by incorporating single-nucleotide polymorphism (SNP) sites.A three-stage analysis was carried out to construct the model and evaluate the diagnostic performance. In stage I, two small cohorts from Xiangya hospital were recruited to validate and identify the detailed regions of collected methylation biomarkers. In stage II, proof-of-concept study cohorts from the Hunan multicenter were recruited to construct a diagnostic tool. In stage III, a blinded cohort comprising suspicious UBC patients was recruited from Beijing single center to further test the robustness of the model.In stage I, single NRN1 exhibited the highest AUC compared with six other biomarkers and the Random Forest model. At the best cutoff value of 5.16, a single NRN1 biomarker gave a diagnosis with a sensitivity of 0.93 and a specificity of 0.97. In stage II, the Random Forest algorithm was applied to construct a diagnostic tool, consisting of NRN1, TERT C228T and FGFR3 p.S249C. The tool exhibited AUC values of 0.953, 0.946 and 0.951 in training, test and all cohorts. At the best cutoff value, the model resulted in a sensitivity of 0.871 and a specificity of 0.947. In stage III, the diagnostic tool achieved a good discrimination in the external validation cohort, with an overall AUC of 0.935, sensitivity of 0.864 and specificity of 0.895. Additionally, the model exhibited a superior sensitivity and comparable specificity compared with conventional cytology and FISH.The diagnostic tool exhibited a highly specific and robust performance. It may be used as a replaceable approach for the detection of UBC.
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