Discovery and validation of new protein biomarkers for urothelial cancer: A prospective analysis. Theodorescu D, Wittke S, Ross MM, Walden M, Conaway M, Just I, Mischak H, Frierson HF, Department of Molecular Physiology, Mellon Prostate Cancer Institute, University of Virginia, Charlottesville, VA

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)561-562
Number of pages2
JournalUrologic Oncology: Seminars and Original Investigations
Volume24
Issue number6
DOIs
Publication statusPublished - Nov 2006

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ASJC Scopus subject areas

  • Oncology
  • Urology

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