Graduate Institute of Integrated Medicine, China Medical University, Taichung 404333, Taiwan.
Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404332, Taiwan.
J Proteome Res. 2021 May 7;20(5):2953-2963. doi: 10.1021/acs.jproteome.1c00164. Epub 2021 Mar 29.
Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.
膀胱癌（UC）是全球第九大常见恶性肿瘤。对于 UC 的监测和诊断，需要具有高准确性的无创且高效的生物标志物。在这项研究中，CKD 患者被作为对照组纳入，以发现 UC 的高度特异性尿蛋白标志物。采用 iTRAQ 标记定量蛋白质组学方法来发现新的潜在标志物。通过 ELISA 检测进一步验证了 501 个样本中的这些标志物，并将其诊断准确性与其他报道的 UC 标志物进行了比较。BRDT、CYBP、GARS 和 HDGF 被鉴定为新型尿 UC 标志物，在包括 CKD 和健康受试者的人群中具有高区分能力。四种新型 UC 标志物的诊断价值优于一组知名或 FDA 批准的尿蛋白标志物 CYFR21.1、Midkine 和 NUMA1。我们发现的三个标志物（BRDT、HDGF、GARS）和一个知名标志物（CYFR21.1）最终被选中并组合成一个标志物组合，用于区分 UC 组和正常组的 AUC 值为 0.962（95%CI，0.94-0.98），用于区分 UC 组和对照组（健康+CKD）的 AUC 值为 0.860（95%CI，0.83-0.89）。
