Discovery and validation of new protein biomarkers for urothelial cancer: a prospective analysis

Lancet Oncol. 2006 Mar;7(3):230-40. doi: 10.1016/S1470-2045(06)70584-8.


Background: Non-invasive methods for diagnosis of urothelial carcinoma have reduced specificity in patients with non-malignant genitourinary disease or other disorders. We aimed to use mass spectrometry and bioinformatics to define and validate a cancer-specific proteomic pattern.

Methods: We used capillary-electrophoresis-coupled mass spectrometry to obtain polypeptide patterns from urine samples of 46 patients with urothelial carcinoma and 33 healthy volunteers. From signatures of polypeptide mass, we established a model for predicting the presence of cancer. The model was refined further by use of 366 urine samples obtained from other healthy volunteers and patients with malignant and non-malignant genitourinary disease. We estimated the proportion of correct classifications from the refined model by applying it to a masked group containing 31 patients with urothelial carcinoma, 11 healthy individuals, and 138 patients with non-malignant genitourinary disease. We also sequenced several diagnostic polypeptides for urothelial carcinoma.

Findings: We identified a diagnostic urothelial-carcinoma pattern of 22 polypeptide masses. On masked assessment, prediction models based on these polypeptides correctly classified all samples of urothelial carcinoma (sensitivity 100% [95% CI 87-100) and all healthy samples (specificity 100% [84-100]). Correct identification of patients with urothelial carcinoma from those with other malignant and non-malignant genitourinary disease ranged from 86% to 100%. A prominent polypeptide from the diagnostic pattern for urothelial carcinoma was identified as fibrinopeptide A-a known biomarker of ovarian cancer and gastric cancer.

Interpretation: Validation of a highly specific biomarker pattern for urothelial carcinoma in a large group of patients with various urological disorders could be used in the diagnosis of other diseases that are identified in urine samples or in other body fluids.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Carcinoma / diagnosis*
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Case-Control Studies
  • Computational Biology
  • Diagnosis, Differential
  • Electrophoresis, Capillary
  • Female
  • Humans
  • Male
  • Mass Spectrometry
  • Proteomics*
  • Sensitivity and Specificity
  • Urologic Neoplasms / diagnosis*
  • Urologic Neoplasms / genetics
  • Urologic Neoplasms / pathology*
  • Urothelium


  • Biomarkers, Tumor