Discovery of Novel Protein Biomarkers in Urine for Diagnosis of Urothelial Cancer Using iTRAQ Proteomics

Chao Jung Chen, Che Yi Chou, Kuo Hsiung Shu, Hung Chun Chen, Ming Cheng Wang, Chia Chu Chang, Bang Gee Hsu, Mai Szu Wu, Yuan Lung Yang, Wen Ling Liao, Chieh Yang, Yu Tien Hsiao, Chiu Ching Huang

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2953-2963
Number of pages11
JournalJournal of Proteome Research
Issue number5
Publication statusPublished - May 7 2021


  • biomarker
  • chronic kidney disease
  • proteomics
  • urine
  • urothelial carcinoma

ASJC Scopus subject areas

  • Biochemistry
  • General Chemistry


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